Gene Editing Pioneers Receive Americas Most Distinguished …

Gene Editing Pioneers Selected to Receive Americas Most Distinguished Prize in Medicine

August 15, 2017 - Albany, NY

For their roles in the creation of a remarkable gene editing system that has been called the discovery of the century, five researchers have been announced as the recipients of the Albany Medical Center Prize in Medicine and Biomedical Research for 2017. All five awardees have made important contributions to the development of CRISPR-Cas9, a gene engineering technology that harnesses a naturally occurring bacterial immune system process. The technology has revolutionized biomedical research and provided new hope for the treatment of genetic diseases and more. The awardees are:

The $500,000 award has been given annually since 2001 to those who have altered the course of medical research and is one of the largest prizes in medicine and science in the United States. It will be awarded on Wednesday, Sept. 27 during a celebration in Albany, New York.

The five recipients were chosen to receive the 2017 Albany Prize for their fundamental and complementary accomplishments related to CRISPR-Cas9. CRISPR is an acronym for clustered regularly interspaced short palindromic repeats, a DNA sequence found in the immune system of simple bacterial organisms.

The discovery of these CRISPR sequences in bacteria in the laboratory was the key to the later development of gene editing technology called CRISPR-Cas9 that has allowed scientists to easily and efficiently edit genes by splicing out and replacing or altering sections of DNA in the cells of any organism, including humans (though most current research uses isolated human cells in labs and animal models only). The editing technique has been compared to cutting and pasting words in a computer program.

CRISPR-Cas9 has revolutionized biological research in tens of thousands of laboratories worldwide. Its potential future applications include the possible ability to cure genetic defects such as muscular dystrophy, eradicate cancer, and allow for pig organs to safely be transplanted into humans. Its uses are so varied that CRISPR is being used to alter butterfly wing patterns and it could also someday help make crops hardier.

Though it cannot be used as a drug in patients yet, it is making a significant impact in the clinical world by accelerating drug research. Additionally, in laboratory experiments, CRISPR-Cas9 is being used to try to modify genes to block the HIV virus, and to attempt to change the DNA of mosquitos that carry the Zika virus so that it cannot be passed to humans.

Rarely has such a recent discovery transformed an entire field of research, as CRISPR has in biological research. Its implications for biological processes, including human health and disease are promising and quite profound, said Vincent Verdile, M.D. 84, the Lynne and Mark Groban, M.D. 69, Distinguished Dean of Albany Medical College and chair of the Albany Prize National Selection Committee. The Albany Prize recognizes that such a significant development in science is brought forth by a community of scientists, and, therefore, we felt it was appropriate to name a larger number of recipients than in the past.

CRISPR is an example of how science in the 21st century often works; as a remarkable ensemble act, in which a cast comes together to produce something that not one of them could do alone.

While most studies focus on gene editing in somatic (non-germline) cells, due to the profound ethical implications of modifying genes and impacting our species and environment, many CRISPR scientists, government representatives, ethicists and the general public are actively debating how we as a society ethically use the technology.

According to Dr. Verdile, the CRISPR story is a testament to the importance of basic biomedical research as the gateway to medical and scientific breakthroughs. The discovery of the CRISPR defense mechanism inside bacteria by basic scientists directly led to the development of the CRISPR gene editing system, which has promise for the treatment of disease.

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2017 Albany Prize Recipients

Emmanuelle Charpentier, Ph.D. Director, Department of Regulation in Infection Biology, Max Planck Institute for Infection Biology, BerlinVisiting Professor, Ume University, Sweden and Honorary Professor, Humboldt University

With her recent groundbreaking findings in the field of RNA-mediated regulation based on the CRISPR-Cas9 system, Dr. Charpentier laid the foundation for the development of the novel, highly versatile and precise genome engineering technology that has revolutionized life sciences research and opens new opportunities for the treatment of genetic disease.

She is co-inventor and co-owner of the fundamental intellectual property comprising the CRISPR-Cas9 technology, and co-founder of CRISPR Therapeutics and ERS Genomics, two companies that are developing the CRISPR-Cas9 genome engineering technology for biotechnological and biomedical applications.

Dr. Charpentier studied biochemistry, microbiology and genetics at the University Pierre and Marie Curie in Paris, and obtained her Ph.D. in microbiology for research performed at the Pasteur Institute in Paris. She continued her work at The Rockefeller University, New York University Langone Medical Center and the Skirball Institute of Biomolecular Medicine, all in New York City, and at St. Jude Childrens Research Hospital in Memphis.

She returned to Europe to establish a research group at the University of Vienna in Austria as assistant and associate professor. She was then appointed associate professor at the Laboratory for Molecular Infection Medicine Sweden at Ume University in Sweden where she is still a visiting professor.

In 2013, she was awarded an Alexander von Humboldt Professorship. She served as the head of the Department of Regulation in Infection Biology at the Helmholtz Centre for Infection Research in Braunschweig and professor at the Medical School of Hannover, Germany. In 2015, she was appointed scientific member of the Max Planck Society and director at the Max Planck Institute for Infection Biology in Berlin.

Jennifer Doudna, Ph.D. Professor, Molecular and Cell Biology and Chemistry, University of California, Berkeley

As an internationally renowned professor of chemistry and molecular and cell biology at U.C. Berkeley, Dr. Doudna and her colleagues rocked the research world in 2012 by describing a simple way of editing the DNA of any organism using an RNA-guided protein found in bacteria. This technology, called CRISPR-Cas9, has opened the floodgates of possibility for human and non-human applications of gene editing, including assisting researchers in the fight against HIV, sickle cell disease and muscular dystrophy.

Dr. Doudna is an investigator with the Howard Hughes Medical Institute and a member of the National Academy of Sciences, the National Academy of Medicine, the National Academy of Inventors and the American Academy of Arts and Sciences. She is also a Foreign Member of the Royal Society, and has received many other honors including the Breakthrough Prize in Life Sciences, the Heineken Prize, the BBVA Foundation Frontiers of Knowledge Award and the Japan Prize.

Dr. Doudna received her Ph.D. from Harvard University and was a postdoctoral research fellow in molecular biology at Harvard Medical School, Massachusetts General Hospital. She was the Lucille P. Markey Scholar in Biomedical Science at the University of Colorado. She later served on the faculty at Yale University as the Henry Ford II Professor of Molecular Biophysics and Biochemistry.

She is the co-author with Sam Sternberg of A Crack in Creation, a personal account of her research and the societal and ethical implications of gene editing.

Luciano A. Marraffini, Ph.D. Associate Professor, Laboratory of Bacteriology, The Rockefeller University, New York City

Dr. Marraffini made the seminal discovery that CRISPR-Cas works by cleaving DNA and was the first to propose that this system could be used for genome editing in heterologous systems. He then collaborated with Feng Zhang to perform the first successful editing experiment in eukaryotic (human) cells using CRISPR-Cas9. He continues to elucidate the molecular mechanisms of the CRISPR-Cas immune response in bacteria, including how sequences of viral and plasmid origin are selected to be integrated into CRISPR arrays and how different CRISPR-Cas systems found in different strains of bacteria attack their targets.Dr. Marraffini received his undergraduate degree from the University of Rosario in Argentina and his Ph.D. from the University of Chicago. He was a postdoctoral fellow at Northwestern University in the laboratory of Erik Sontheimer, after which he joined The Rockefeller University as assistant professor and the head of the Laboratory of Bacteriology in 2010. He was named a Howard Hughes Medical Institute-Simons Faculty Scholar in 2016. He is a recipient of the 2015 Hans Sigrist Prize and was named a finalist in the life sciences by the 2015 Blavatnik National Awards for Young Scientists. In 2014, Cell named him one of its 40 Under 40. He is a 2012 Rita Allen Foundation Scholar and a 2011 Searle Scholar, and is the recipient of an NIH Directors New Innovator Award and an RNA Society Award.

Francisco J.M. Mojica, Ph.D.Associate Professor of Microbiology, Department of Physiology, Genetics and Microbiology, University of Alicante, SpainMember of the Multidisciplinary Institute for the Study of the Environment Ramn Margalef, Spain

Dr. Mojicas pioneering work on CRISPR and his fundamental contribution to the knowledge of these components of bacteria for more than two decades makes him a leading scholar on the subject. Thanks to the contributions of Dr. Mojica in this field, exceptional laboratory tools, known as CRISPR-Cas technology, have been developed that can be used for the genetic manipulation of any living being, including humans. This technology has greatly simplified research in biology and medicine, for example, to study complex genetic processes such as those involved in embryonic development, carcinogenesis or neurodegenerative disorders. It is postulated that CRISPR-Cas technology will allow, in the near future, to cure diseases that are not curable or very difficult to tackle.

He received his Ph.D. in Biotechnology from the University of Alicante. He later completed two postdoctoral fellowships in laboratories at the University of Utah, Salt Lake City, and Oxford University in Great Britain. In 1997, he became professor of microbiology at the University of Alicante, founding the research group in molecular microbiology to resume the study on CRISPR he had initiated during his Ph.D. thesis work. In the last few years, his investigation has focused on the CRISPR immunization process, to understand how bacteria acquire foreign genetic material that make them resistant to infecting agents.

He has received many honors including the Lilly Foundation Award for Preclinical Biomedical Research, the Rey Jaime I Prize for Basic Research, and the BBVA Foundation Frontiers of Knowledge Award (biomedicine category).Feng Zhang, Ph.D.Core Member, Broad Institute of MIT and HarvardInvestigator at the McGovern Institute for Brain Research at MITThe James and Patricia Poitras Professor in Neuroscience and Associate Professor, Departments of Brain and Cognitive Sciences and Biological Engineering, Massachusetts Institute of Technology, Cambridge, Mass.

Dr. Zhang is a bioengineer developing and applying novel molecular technologies for studying the molecular and genetic basis of diseases and providing treatment. He played a seminal role in developing optogenetics, a powerful technology for dissecting neural circuits using light. Since joining the Broad and McGovern institutes in January 2011, Zhang has pioneered the development of genome editing tools for use in eukaryotic cells including human cells from natural microbial CRISPR systems.

Following his landmark demonstration that CRISPR-Cas9 could be harnessed for mammalian genome editing, his lab has continued to explore the CRISPR system and develop novel technologies for perturbing and editing the genome for disease research. He and his colleagues have successfully harnessed two additional CRISPR systems: CRISPR-Cpf1, which may allow simpler and more precise genome engineering, and CRISPR-Cas13a, a novel RNA-targeting system, which his team has adapted for use in rapid diagnostics.

Zhang leverages CRISPR and other methods to study the genetics and epigenetics of human diseases, especially complex disorders, such as psychiatric and neurological diseases, that are caused by multiple genetic and environmental risk factors and which are difficult to model using conventional methods. His labs tools, which he has made widely available, are also being used in the fields of immunology, clinical medicine, and cancer biology, among others. His long-term goal is to develop novel therapeutic strategies for disease treatment.He received his A.B. in chemistry and physics from Harvard College and his Ph.D. in chemistry from Stanford University.

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The Albany Medical Center Prize was established in 2000 by the late Morris Marty Silverman, a New York City businessman and philanthropist who grew up in Troy, N.Y., to honor scientists whose work has demonstrated significant outcomes that offer medical value of national or international importance. A $50 million gift commitment from the Marty and Dorothy Silverman Foundation provides for the prize to be awarded annually for 100 years.

Three previous Nobel Prize winners have been among the ranks of researchers honored, and five Albany Prize recipients have gone on to win the Nobel Prize, including Shinya Yamanaka, M.D., Ph.D., a leading stem cell scientist; Elizabeth Blackburn, Ph.D., who discovered the molecular nature of telomeres; Bruce Beutler, M.D., and the late Ralph Steinman, M.D., for their discoveries regarding the detailed workings of the immune system; and Robert Lefkowitz, M.D., for his work on cell receptors.

For biographies and downloadable photos of the 2017 recipients, and more information on the Albany Medical Center Prize in Medicine and Biomedical Research, visit: http://www.amc.edu/Academic/AlbanyPrize.

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Media Inquiries:

Sue Ford Rajchel

fords@mail.amc.edu

(518) 262 - 3421

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Resveratrol Lift Firming Serum – Caudalie | Sephora

Which skin type is it good for? Normal Oily Combination Dry Sensitive

What it is:A resculpting treatment serum to reshape, define, and lift the look of skin for a youthful appearance.

Solutions for:- Fine lines and wrinkles- Loss of firmness and elasticity- Dryness

If you want to know moreThis oil-free, innovative resculpting serum is formulated with Caudalie's new breakthrough patent of stabilized vine resveratrol (for firmness) and micro hyaluronic acids (for volume) to visibly recontour, refirm, and replump aging skin. For the first time, these molecules' synergy is being harnessed to support skin's natural production of hyaluronic acid, so the skin is plumped from within. The formula is further enriched with a peptide composition that works on natural collagen and elastin to lift the look of facial contours and reduce visible effects of aging. The light, hydrating texture blends into the skin without any sticky residue and can be applied under makeup.

What it is formulated WITHOUT:- Parabens- Sulfates- Phthalates

What else you need to know:Resveratrol Lift Firming Serum is winner of a Womens Health 2017 Beauty Award.

Research has unveiled a surprising synergy between a molecule from grapevine called resveratrol, and a complex of micro hyaluronic acids. While each ingredient is effective on its own, the combination is a breakthrough because it helps support the skin's own production of natural hyaluronic acid. Hyaluronic acid is naturally present in the skin and plays an important role in hydration and preservation. A decrease in hyaluronic acid quantity and quality with age leads to dryness and the appearance of wrinkles. Caudalie's new patented complex helps support the skin to make its own natural hylauronic acid. This product is noncomedogenic and tested under dermatological supervision.

Research results:% of satisfaction, 100 people, 7 days: - 80% of testers reported denser skin

% of satisfaction, 100 people, 28 days: - 91% of testers reported firmer skin- 76% of testers reported lifted skin

% of satisfaction, 33 people, 56 days: - 85% of testers reported smoothed wrinkles

Continued here:

Resveratrol Lift Firming Serum - Caudalie | Sephora

Irinotecan – Wikipedia

IrinotecanClinical dataTrade namesCamptosar (US), Campto (EU), Onivyde (liposomal)AHFS/Drugs.comMonographMedlinePlusa608043Pregnancycategory

O=C7OCC=6C(=O)N2C(c1nc5c(c(c1C2)CC)cc(OC(=O)N4CCC(N3CCCCC3)CC4)cc5)=C/C=6[C@@]7(O)CC

Irinotecan, sold under the brand name Camptosar among others, is a medication used to treat colon cancer and small cell lung cancer.[1] For colon cancer it is used either alone or with fluorouracil.[1] For small cell lung cancer it is used with cisplatin.[1] It is given by slow injection into a vein.[1]

Common side effects include diarrhea, vomiting, bone marrow suppression, hair loss, shortness of breath, and fever.[1] Other severe side effects include blood clots, colon inflammation, and allergic reactions.[1] Those with two copies of the UGT1A1*28 gene variant are at higher risk for side effects.[1] Use during pregnancy can result in harm to the baby.[1] Irinotecan is in topoisomerase inhibitor family of medication.[2] It works by blocking topoisomerase 1 which results in DNA damage and cell death.[1]

Irinotecan was approved for medical use in the United States in 1996.[1] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[3] In the United Kingdom it is available as a generic medication and costs the NHS about 114.00 pounds per 100mg.[2] It is made from the natural compound camptothecin.[1]

Its main use is in colon cancer, in particular, in combination with other chemotherapy agents. This includes the regimen FOLFIRI, which consists of infusional 5-fluorouracil, leucovorin, and irinotecan. The regimen XELIRI consists of capecitabine and irinotecan.[4][5]

The most significant adverse effects of irinotecan are severe diarrhea and extreme suppression of the immune system.[6]

Irinotecan-associated diarrhea is severe and clinically significant, sometimes leading to severe dehydration requiring hospitalization or intensive care unit admission. This side-effect is managed with the aggressive use of antidiarrheals such as loperamide or co-phenotrope with the first loose bowel movement.

The immune system is adversely impacted by irinotecan. This is reflected in dramatically lowered white blood cell counts in the blood, in particular the neutrophils. The patient may experience a period of neutropenia (a clinically significant decrease of neutrophils in the blood) while the bone marrow increases white cell production to compensate.

Irinotecan is activated by hydrolysis to SN-38, an inhibitor of topoisomerase I. This is then inactivated by glucuronidation by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). The inhibition of topoisomerase I by the active metabolite SN-38 eventually leads to inhibition of both DNA replication and transcription.[6]

The molecular action of irinotecan occurs by trapping a subset of topoisomerase-1-DNA cleavage complexes, those with a guanine +1 in the DNA sequence.[7] One irinotecan molecule stacks against the base pairs flanking the topoisomerase-induced cleavage site and poisons (inactivates) the topoisomerase 1 enzyme.[7]

Click on genes, proteins and metabolites below to link to respective articles. [ 1]

Irinotecan is converted by an enzyme into its active metabolite SN-38, which is in turn inactivated by the enzyme UGT1A1 by glucuronidation.

People with variants of the UGT1A1 called TA7, also known as the "*28 variant", express fewer UGT1A1 enzymes in their liver and often have Gilbert's syndrome. During chemotherapy, they effectively receive a larger than expected dose because their bodies are not able to clear irinotecan as fast as others. In studies this corresponds to higher incidences of severe neutropenia and diarrhea.[8]

In 2004, a clinical study was performed that both validated prospectively the association of the *28 variant with greater toxicity and the ability of genetic testing in predicting that toxicity before chemotherapy administration.[8]

In 2005, the FDA made changes to the labeling of irinotecan to add pharmacogenomics recommendations, such that irinotecan recipients with a homozygous (both of the two gene copies) polymorphism in UGT1A1 gene, to be specific, the *28 variant, should be considered for reduced drug doses.[9] Irinotecan is one of the first widely used chemotherapy agents that is dosed according to the recipient's genotype.[10]

Irinotecan received accelerated approval from the U.S. Food and Drug Administration (FDA) in 1996 and full approval in 1998.[11][12]

During development, it was known as CPT-11.

A liposome encapsulated version of irinotecan sold as Onivyde, was approved by FDA in October 2015 to treat metastatic pancreatic cancer.[13] It gained EU approval in October 2016.[14]

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Irinotecan - Wikipedia

Resveratrol Lift Eye Lifting Balm – Caudalie | Sephora

Which skin type is it good for? Normal Oily Combination Dry Sensitive

What it is:An innovative, natural eye balm with a breakthrough patent to lift and smooth the areas around the eyes and lips.

Solutions for:- Fine lines and wrinkles- Loss of firmness and elasticity- Dryness

If you want to know moreThis cutting-edge eye balm is powered by a patent combining vine resveratrol with micro hyaluronic acids for an unparalleled age-reversing effect. Formulated with advanced peptides and an anti-puffiness plant complex, this eye balm helps lift the look of eyelids, reduce puffiness and dark circles, and smooth the appearance of wrinkles. The texture is silky and melts into skin without the use of synthetic emulsifiersand it works especially well under makeup.

What it is formulated WITHOUT:- Parabens- Sulfates- Phthalates

What else you need to know:Research has unveiled a surprising synergy between a molecule from grapevine called resveratrol, and a complex of micro hyaluronic acids. While each ingredient is effective on its own, the combination is a breakthrough because it helps support the skin's own production of natural hyaluronic acid. Hyaluronic acid is naturally present in the skin and plays an important role in hydration and preservation. A decrease in hyaluronic acid quantity and quality with age leads to dryness and the appearance of wrinkles. Caudalie's new patented complex helps support the skin to make its own natural hyaluronic acid. This fragrance-free product is opthamologist approved for use around the entire eye area, and suitable for sensitive skin and contact lens wearers.

"This natural eye balm is powered by a patent combining vine resveratrol with hyaluronic acid for an age-reversing effect. Formulated with advanced peptides and an anti-puffiness plant complex, this eye balm helps lift the skin of the eyelids, reduce puffiness and dark circles, and smooth the appearance of wrinkles. The texture is silky and melts into skin without the use of synthetic emulsifiers, and it works especially well under makeup.""Dermatologist Karen Hammerman, MD, of Schweiger Dermatology Group

Research results:In a satisfaction test on 100 people, after 28 days:- 80% of testers reported a reduction in under-eye puffiness

Originally posted here:

Resveratrol Lift Eye Lifting Balm - Caudalie | Sephora

Neurology Associates of Arlington, P.A.

For news and announcements please see the Bulletin Board on the home page of our patient portal.

We are a neurology group that has served Arlington, Mansfield, Grand Prairie, and surrounding areas since 1983. Our services include diagnosis, treatment, and clinical research. We use electronic medical records and provide a patient portal.

To Schedule an Appointment

To schedule an appointment call (817) 225-0410. New patients will be scheduled by our new patient scheduler.

Physician Referrals

Physicians may refer patients by telephone or facsimile.

Address and Phone

2800 E. Broad Street, Suite 504

Mansfield, TX 76063

Phone (817) 225-0410

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Monday - Friday: 8:00 - 5:00 pm.

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Consultation and treatment

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Centers of Excellence

Our offices are in the professional office building on the east side of Methodist Mansfield Medical Center, at the corner of East Broad Street and North Miller Road. Parking is free.

Neurology Associates of Arlington, P.A.

Dedicated to the diagnosis and treatment of patients who have neurological disorders

Conditions We Treat

Headaches

Back and neck problems

Carpal tunnel syndrome

Sleep disorders

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Other neurological disorders

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Neurology Associates of Arlington, P.A.

Ethical Implications of Human Genetic Engineering | SAGE

DNA editing techniques have been available for decades and are crucial tools for understanding gene functions and molecular pathways. Recently, genome editing has stepped back into the limelight because of newer technologies that can quickly and efficiently modify genomes by introducing or genetically correcting mutations in human cells and animal models. These tools include Zinc Finger Nucleases (ZFNs), Transcription activator-like effector nucleases (TALENs), and the most recent player to join the ranks, Clustered Regularly Interspaced Short Palindromic repeats (CRISPR) (here, here). In a short time span, CRISPR/Cas9 has completely revolutionized the understanding of protein function, disease modeling, and potential therapeutic applications.

BACKGROUND on CRISPR/Cas9

The CRISPR/Cas9 system functions similarly to ZFNs and TALENs, it also takes advantage of a cells DNA repair machinery to delete (knock-out) or add in (knock-in) sequences of DNA. However, CRISPR/Cas9 offers several advantages: it is easier to target a specific gene of interest since designing the required CRISPR component is simple and efficient, whereas generating ZFNs and TALENs is more time consuming; it is often more proficient in generating the desired recombination results; and it is exponentially more cost effective, so almost any laboratory in the world can use it. CRISPR/Cas9 has been shown to work in several model organisms, and consequently researchers are keen to apply this technology for modifying genetic mutations in humans with uncured diseases as well as in human embryos, which arouses many scientific and ethical considerations.

Human embryonic gene editing

Genome editing technologies have come a long way and have already advanced towards mammalian models and clinical trials in humans. Recently, genetic modification of human embryos using CRISPR/Cas9 technology was achieved by the Huang laboratory in China in April 2015. They genetically modified un-viable embryos obtained from an in vitro fertilization clinic. These embryos were fertilized with two different sources of sperm, thus impairing their development. In this study, the Huang group repaired a mutation in the human -globin gene (HBB) that causes the blood disorder -thalassaemia. The CRISPR/Cas9 system and a donor DNA sequence containing the normal, healthy version of the HBB were injected into 86 embryos. A total of four embryos successfully integrated the corrected version of the HBB at the appropriate site. However, the authors reported a high number of off-target effects, meaning that CRISPR/Cas9 modified other locations in the genome; a non-ideal situation that could cause the disruption of other essential gene functions. The study demonstrated two important findings: genetic engineering is possible in human embryos and the CRISPR/Cas9 system requires essential improvements before it can be used in future studies on human embryos. More importantly, these results force scientists to question the future and the implications of such a powerful technology. Should we accept genetic engineering of human embryos? If yes, when and in what capacity should we accept it?

Current guidelines and regulation

Scientists in the United States are addressing the need for regulation of human embryonic gene editing. On April 29th, the US National Institute of Health (NIH) director, Dr. Francis Collins, released a statement emphasizing the bureaus policy against funding research involving genome editing of human embryos and the ethical concerns regarding this technology. However, the policy does not necessarily cover privately funded projects.

Safety regarding genetic engineering is a major concern and Huangs publication highlights this point. However, this publication forces the community to address whether scientists should use non-viable or discarded embryos to improve the efficiency and efficacy of the CRISPR/Cas9 system. The CRISPR/Cas9 system was developed for human genome targeting in 2012 and since then has seen rapid improvements. If it is decided that unviable embryos can be used for this type of research, the next step for US lawmakers is to evaluate new guidelines for the funding and safety of genetic engineering in these embryos.

Ethical concerns

While the interest and use of CRISPR/Cas9 has exploded since its discovery in 2012, prominent scientists in the field have already initiated conversations regarding the ethical implications that arise when modifying the human genome. Preventing genetic diseases by human genetic engineering is inevitable. The slippery slope is when/if we start to use it for cosmetic changes such as eye color or for improving a desired athletic trait. A perfect example is surgery, which we have performed for hundred years for disease purposes and is now widely used as a cosmetic tool. Opening the doors for genetic engineering of human embryos could with time lead to manipulate genetics for desirable traits, raising the fear of creating a eugenic driven human population.

Who are we to manipulate nature? However, for all those who suffer from genetic diseases the answer is not so simples; if we can safely prevent severe genetic diseases and create healthy humans, why not manipulate nature? Have we not already done this in other animal populations? At this time the long term effects of genome editing remain unknown, raising additional questions. As the field progresses, with appropriate regulations and guidelines it will eventually co-exist alongside other major controversial topics including nuclear power and genetically modified organisms. Since ethics are different across the world, creating international guidelines will be a challenge, but a necessity. Strict regulations are in place for nuclear power, the same should be possible for genetic engineering of human embryos. To outlaw genetic engineering entirely will be potentially declining a place at the discussion table, as the further utilization of CRISPR/Cas9 technology is unlikely to be abandoned.

This fall The National Academy of Sciences and National Academy of Medicine, together with CRISPR/Cas9 discoverers Dr. Jennifer Doudna, Dr. Emmanuelle Charpentier, and other leading scientist within the field are organizing an international summit to consider all aspects (both ethical and scientific) of human genetic engineering to develop standard guidelines and policies for practicing human genome editing. The NIH already has guidelines in place, and will potentially add more as a result of this summit. It is expected that other countries will have varying guidelines for human genomic engineering. Also, to avoid fear and misunderstanding, scientists will need to convey human genome editing in a responsible manner to the general human population. This summit is a step in the right direction encouraging caution and regulations. Hence, there is now a need for a timely but thoughtful set of guidelines for the general scientific community as well as for the broader human community.

Read this article:
Ethical Implications of Human Genetic Engineering | SAGE

Resveratrolthe hype continues – Harvard Health Blog …

Oh, the giddy abandon that overtakes some headline writers when crowning a story about resveratrol, a chemical found in red wine. Heres a sampling of the latest:

All that for an article published today in the journal Cell suggesting that resveratrol blocks the action of a muscle enzyme called phosphodiesterase 4 in mice. Dont get me wrong: its interesting research, that couldemphasis on couldopen the door someday to new treatments for heart disease, diabetes, memory loss, and other chronic conditions. But it doesnt merit the hype that comes with almost any new research on resveratrol.

Resveratrol is a compound that various plants make to fight off bacteria, fungi, and other microbial attackers, or to withstand drought or lack of nutrients. It has been found in red and purple grapes, blueberries, cranberries, mulberries, lingonberries, peanuts, and pistachios. Resveratrol is also abundant in the roots of Japanese knotweed, a plant that has become a hard-to-eradicate invader in the United States.

In 1992, two Cornell University plant scientists suggested that resveratrol might be responsible for the cardiovascular benefits of red wine. Since then, hundreds of reports have indicated that resveratrol mayemphasis on mayprotect against cancer, cardiovascular disease, vascular dementia, and Alzheimers disease, and extend the life span.

Exactly how resveratrol might do all this is still a mystery. One possibility is that it turns on genes that make sirtuins, ancient proteins found in virtually all species. Activating sirtuins kicks off a response that fights disease and prolongs life. The Cell researchers were trying to figure out just how resveratrol might turn on sirtuin genes.

Virtually all of the positive studies on resveratrol have come from cultures of cells or laboratory experiments with yeast, roundworms, fruit flies, the short-lived turquoise killifish, or mice. The few human studies have looked at specific intermediate markers, such as levels of antioxidants, heart rate variability, blood flow to the brain, and amounts of cancer proteins. None have measured long-term health or survival.

Another big unknown is side effects. Resveratrol acts on many different tissues in the body. It is chemically related to estrogen. In some situations, high doses of resveratrol boost the activity of estrogen, in others they block estrogen. That makes resveratrol supplements iffy for women with cancer of the breast, ovary, uterus, or other estrogen-sensitive tissue, those trying to become pregnant, or those taking an oral contraceptive.

Resveratrol makes platelets in the bloodstream less sticky, and so could increase the risk of bleeding in people who take warfarin (Coumadin), clopidogrel (Plavix), aspirin, ibuprofen, or other nonsteroidal anti-inflammatory drugs.

Another cloud: a company called Sirtris Pharmaceuticals, which was established to develop drugs from resveratrol, pulled the plug on the program in 2010 when a clinical trial showed that one of these drugs might be linked to kidney damage.

If you believe that resveratrol will help you live longer and healthier, get it from food or wine, not by choking down resveratrol pills. Why? Eating red grapes, blueberries, and pistachios, or having a glass of your favorite red wine, are pleasurable ways to take in resveratrol. Plus you get all the other healthful plant products that come with the resveratrol. Getting it via supplement is dull, and you cant always trust what you are getting. If you choose to take a supplement, shop carefully. A review by the independent ConsumerLab found that one brand cost just 15 cents per 100 milligrams of resveratrol, while another cost $2.76 per 100 milligrams.

Its worth keeping an eye on resveratrol research. But its far too soon to be promoting it as a fountain of youth or wonder drug.

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Resveratrolthe hype continues - Harvard Health Blog ...

Stanford Biochemistry

The Department of Biochemistry was founded in 1959 when Arthur Kornberg was recruited as a fundamental part of the move of the Stanford Medical School from San Francisco to the main Stanford campus. Innovations established at that time included the mixing of students and postdoctoral fellows in common laboratories so that the different research groups would be familiar with each other's research work and cross-fertilization would be inevitable. Specialized reagents were shared and major instruments were made available to everyone. Benches were not owned by a particular faculty member, but fair and equitable sharing of space was enjoyed in an unprecedented way of carrying out research in a department setting. We have embraced and maintained these approaches over time, and everyone in the department continues to prosper under this unusual innovative mode of operation, rarely found anywhere else in the world.

In the first decade of the department, there was a nearly complete focus on DNA and RNA biochemistry, and methodologies were also focused on hard-core biochemical approaches of enzyme purification and characterization. The current department is now enormously diverse with nearly everyone using interdisciplinary approaches of biochemistry, genetics, biophysics, structural biology, high-resolution light microscopy, and other innovative methodologies, often developed by Biochemistry students and postdoctoral fellows during the course of their work. Thus, genetic engineering, high-throughput RNA expression analysis, and single molecule analysis all came out of the Biochemistry Department and are fueling current advances in biosciences, biotechnology and medicine.

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Stanford Biochemistry

Hormone Replacement Therapy | Hormonal Imbalance Treatment

Palm Springs Life Extension Institute is the only clinic in the country that owns a U.S. Patent for growth hormone and other bio-identical hormone replacements. It is the only clinic that offers a $25,000 Cash Reward for anyone who has a difference between their chronological age (birth date) and their biological age as measured by a DNA-TELOMERE test. Many of its patients, including the founder, Dr. Edmund Chein, M.D. have accomplished this miraculous feat.As the only clinic in the U.S. that specializes in Longevity Medicine, the cliniccures menopause, andropause, atherosclerosis, elevated cholesterol, and hypertension without drugs or pharmaceuticals. It cures these diseases with bio-identical hormones and nutrition. It treats the cause of the disease and cures it rather than controlling the disease with pharmaceuticals.WHAT IS BIO-IDENTICAL HORMONE REPLACEMENT THERAPY?

It is the use of bio-identical hormones and nutrition to cure and eliminate age related diseases such as hypertension, cholesterol elevation, osteoporosis, menopause, andropause, erectile dysfunction, atherosclerosis, dementia and Alzheimers disease.

Hormones are emails, faxes and letters between organs in the body. Bio-identical hormone replacement therapy, including the use of Growth Hormone, is safe because the doctors simply replace the levels to the levels you had them when you were in your 20s. We do NOT push the levels beyond the physiological maximum of a 20 year old (like what the therletes do- which is why Testosterone became a controlled substance and estrogen is not). If one did not get any side effects when they were 20 years old, why would they get any side effects when they hormone levels return to a 20 year old level? In doing so, your aging process is slowed down, your biological age is reversed, andyour life expectancy is prolonged as a natural consequence. Age related diseases arecured. Menopause and Andropause are eliminated

The need for bio-identical hormone replacement therapy is established by blood or saliva tests. When the levels of the hormones are not OPTIMAL, one needs replacement, regardless of the age. The reference range is again that of a 20 year old, NOT that of a 60 year old. (The reason is we do not want the age related diseases associated with the 60 year olds. Otherwise, it would be normal to have hypertension, elevated cholesterol, diabetes, and atherosclerosis). Any who has optimal hormone levels thus do not need replacement.

There are many products and therapies in the world that claim to do the above. But no product, its owner, or its inventor had put their biological age as measured by any means- including telomere ( the most scientific one) on the web to show that the owner, manufacturer, or the inventor had succeeded in achieving biological age reversal, a necessary PREREQUISITE for extending health span or life span. Palm Springs Life Extension Institute is the only clinic that not only achieved this, but offers a $25,000 cash reward for anyone who can beat our achievement.

Check out Dr. Cheins peer reviewed 2,000 human subject study publication that he did with Dr. Cass Terry of Medical College of Wisconsin. Check out his status as the first physician in the USA to use Growth Hormone for replacement in adults, his other medical inventions, his books, and the videos on YouTube. Get In Touch with us to get the complete guidance regarding our products and services.

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Hormone Replacement Therapy | Hormonal Imbalance Treatment

Sirtuin – Wikipedia

Sirtuins are a class of proteins that possess either mono-ADP-ribosyltransferase, or deacylase activity, including deacetylase, desuccinylase, demalonylase, demyristoylase and depalmitoylase activity.[2][3][4][5][6] Sirtuins regulate important biological pathways in bacteria, archaea and eukaryotes. The name Sir2 comes from the yeast gene 'silent mating-type information regulation 2',[7] the gene responsible for cellular regulation in yeast.

Sirtuins have been implicated in influencing a wide range of cellular processes like aging, transcription, apoptosis, inflammation[8] and stress resistance, as well as energy efficiency and alertness during low-calorie situations.[9] Sirtuins can also control circadian clocks and mitochondrial biogenesis.

Yeast Sir2 and some, but not all, sirtuins are protein deacetylases. Unlike other known protein deacetylases, which simply hydrolyze acetyl-lysine residues, the sirtuin-mediated deacetylation reaction couples lysine deacetylation to NAD hydrolysis. This hydrolysis yields O-acetyl-ADP-ribose, the deacetylated substrate and nicotinamide, itself an inhibitor of sirtuin activity. The dependence of sirtuins on NAD links their enzymatic activity directly to the energy status of the cell via the cellular NAD:NADH ratio, the absolute levels of NAD, NADH or nicotinamide or a combination of these variables.

Whereas bacteria and archaea encode either one or two sirtuins, eukaryotes encode several sirtuins in their genomes. In yeast, roundworms, and fruitflies, sir2 is the name of one of the sirtuin-type proteins (see table below).[10] This research started in 1991 by Leonard Guarente of MIT.[11][12] Mammals possess seven sirtuins (SIRT17) that occupy different subcellular compartments such as the nucleus (SIRT1, -2, -6, -7), cytoplasm (SIRT1 and SIRT2) and the mitochondria (SIRT3, -4 and -5).

The first sirtuin was identified in yeast (a lower eukaryote) and named sir2. In more complex mammals, there are seven known enzymes that act in cellular regulation, as sir2 does in yeast. These genes are designated as belonging to different classes (I-IV), depending on their amino acid sequence structure.[13][14] Several Gram positive prokaryotes as well as the Gram negative hyperthermophilic bacterium Thermotoga maritima possess sirtuins that are intermediate in sequence between classes and these are placed in the "undifferentiated" or "U" class.[13] In addition, several Gram positive bacteria, including Staphylococcus aureus and Streptococcus pyogenes, as well as several fungi carry macrodomain-linked sirtuins (termed "class M" sirtuins).[6] Most notable, the latter have an altered catalytic residue, which make them exclusive ADP-ribosyl transferases.

Sirtuin list based on North/Verdin diagram.[17]

Sirtuin activity is inhibited by nicotinamide, which binds to a specific receptor site,[18] so it is thought that drugs that interfere with this binding should increase sirtuin activity. Development of new agents that would specifically block the nicotinamide-binding site could provide an avenue for development of newer agents to treat degenerative diseases such as cancer, diabetes, atherosclerosis, and gout.[19][20]

Sirtuins have been proposed as a therapeutic target for type II diabetes mellitus.[21]

Preliminary studies with resveratrol, a possible SIRT1 activator, have led some scientists to speculate that resveratrol may extend lifespan.[22] Further experiments conducted by Rafael de Cabo et al. showed that resveratrol-mimicking drugs such as SRT1720 could extend the lifespan of obese mice by 44%.[23] Comparable molecules are now undergoing clinical trials in humans.

Cell culture research into the behaviour of the human sirtuin SIRT1 shows that it behaves like the yeast sirtuin Sir2: SIRT2 assists in the repair of DNA and regulates genes that undergo altered expression with age.[24] Adding resveratrol to the diet of mice inhibit gene expression profiles associated with muscle aging and age-related cardiac dysfunction.[25]

A study performed on transgenic mice overexpressing SIRT6, showed an increased lifespan of about 15% in males. The transgenic males displayed lower serum levels of insulin-like growth factor 1 (IGF1) and changes in its metabolism, which may have contributed to the increased lifespan.[26]

SIRT1, SIRT6 and SIRT7 proteins are employed in DNA repair.[27] SIRT1 protein promotes homologous recombination in human cells and is involved in recombinational repair of DNA breaks.[28]

SIRT6 is a chromatin-associated protein and in mammalian cells is required for base excision repair of DNA damage.[29] SIRT6 deficiency in mice leads to a degenerative aging-like phenotype.[29] In addition, SIRT6 promotes the repair of DNA double-strand breaks.[30] Furthermore, over-expression of SIRT6 can stimulate homologous recombinational repair.[31]

SIRT7 knockout mice display features of premature aging.[32] SIRT7 protein is required for repair of double-strand breaks by non-homologous end joining.[32]

These findings suggest that SIRT1, SIRT6 and SIRT7 facilitate DNA repair and that this repair slows the aging process (see DNA damage theory of aging).

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Sirtuin - Wikipedia

Integrative Medicine – 9780323358682 | US Elsevier Health …

Part I INTEGRATIVE MEDICINE

1. The Philosophy of Integrative Medicine

2. Creating Optimal Healing Environments

3. The Healing Encounter

4. The Whole Health Process

Part II INTEGRATIVE APPROACH TO DISEASE

Section 1. Affective Disorders

5. Depression

6. Anxiety

7. Attention Deficit Disorder

8. Autism Spectrum Disorder

9. Insomnia

10. Posttraumatic Stress Disorder (PTSD)

Section 2. Neurology

11. Alzheimer's Disease

12. Headache

13. Peripheral Neuropathy

14. Multiple Sclerosis

15. Parkinson's Disease

Section 3. Infectious Disease

16. Otitis Media

17. Chronic Sinusitis

18. Viral Upper Respiratory Infection

19. HIV/AIDS

20. Herpes Simplex Virus

21. Chronic Hepatitis

22. Urinary Tract Infection (UTI)

23. Lyme Disease

Section 4. Cardiovascular Disease

24. Hypertension

25. Heart Failure

26. Coronary Artery Disease

27. Dyslipidemia

28. Cardiac Arrhythmia

Section 5. Allergy/Intolerance

29. Asthma

30. The Allergic Patient

31. Food Allergy and Intolerance

Section 6. Metabolic/Endocrine Disorders

32. Insulin Resistance and the Metabolic Syndrome

33. Diabetes Mellitus

34. Hypothyroidism

35. Polycystic Ovarian Syndrome

36. Osteoporosis

37. Obesity

38. MTHFR, Homocysteine and Nutrient Needs

39. Adrenal Fatigue

Section 7. Nephrology

40. Chronic Kidney Disease

Section 8. Gastrointestinal Disorders

41. Irritable Bowel Syndrome

42. Gastroesophageal Reflux Disease

43. Peptic Ulcer Disease

44. Cholelithiasis

45. Recurring Abdominal Pain in Pediatrics

46. Constipation

Section 9. Autoimmune Disorders

47. Fibromyalgia

48. Chronic Fatigue Syndrome

49. Rheumatoid Arthritis

50. Inflammatory Bowel Disease

Section 10. Obstetrics/Gynecology

51. Preconception Counseling and Fertility

52. Labor Pain Management

53. Postdates Pregnancy

54. Nausea and Vomiting in Pregnancy

55. Menopause

56. Premenstrual Syndrome

57. Dysmenorrhea

58. Leiomyomata

59. Vaginal Dryness

Section 11. Urology

60. Benign Prostatic Hyperplasia

61. Urolithiasis

62. Chronic Prostatitis

63. Erectile Dysfunction

64. Testosterone Deficiency

Section 12. Musculoskeletal

65. Osteoarthritis

66. Myofascial Pain Syndrome

67. Chronic Low Back Pain

68. Neck Pain

69. Gout

70. Carpal Tunnel Syndrome

71. Epicondylosis

Section 13. Dermatology

72. Atopic Dermatitis

73. Psoriasis

74. Urticaria

75. Aphthous Stomatitis

76. Seborrheic Dermatitis

77. Acne/Rosacea

Section 14. Cancer

78. Breast Cancer

79. Lung Cancer

80. Prostate Cancer

81. Colon Cancer

82. Palliative and End of Life Care

Section 15. Substance Abuse

83. Alcoholism and Substance Abuse

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Integrative Medicine - 9780323358682 | US Elsevier Health ...

Extreme genetic engineering and the human future – Friends …

On the eve of the U.S. National Academies of Sciences and MedicineInternational Summit on Human Gene Editing, theCenter for Genetics and Societyand Friends of the Earth released a new report Extreme Genetic Engineering and the Human Future: Reclaiming Emerging Biotechnologies for the Common Good.

Read thefullreportor theexecutive summary.

Read thenews release.

Summary: Recent research in genetic engineering and synthetic biology has enabled scientists to artificially redesign life everything from microbes to people. Amid the breakneck speed of recent developments in genetic engineering and synthetic biology that could be used to alter human DNA, this report examines health, regulatory, social and ethical questions about proposals ranging from genetically altering human gut bacteria to implementing germline editing altering human embryos and reproductive cells to produce permanent, hereditary genetic modification of future children and generations. It also examines the systemic and commercial incentives to rush newly discovered biotechnologies to market, regardless of their social utility and ahead of appropriate, transparent assessment and oversight.

The report calls for:

BackgroundEmerging biotechnologies are enabling researchers and corporations to control and manipulate the basic building blocks of life. The impacts of these technologies are already rippling through society, as corporations patent our genes and those of other organisms.

Researchershail synthetic biologya new set of extreme genetic engineering techniques as the future of manufacturing, engineering and medicine. Some of these techniques have also brought the prospect of genetically engineered humans closer to reality.

In April 2015, researchers from Sun Yat-sen University reported that they had used gene editing techniques toalter human embryos, thefirst time in historythis is known to have occurred. In September 2015, a group of six major UK research funders and theHinxton Group, an international consortium on stem cells and ethics, both released statements advocating for gene editing research in human embryos.

Recent genetic engineering discussions have focused onCRISPR/Cas9, a molecular complex intended to edit a genome by cutting out and/or splicing in parts of DNA sequences. This technique (which is not yet perfected, but is rapidly being refined) has been promoted as a promising tool to prevent genetic diseases. But, if used to modify embryos, it could result in permanent, heritable changes to future generations.

Risks and concernsThere are significant scientific, environmental, health and ethical challenges to the human applications of synthetic biology, which currently include reengineering the human microbiome, gene drives, xenotransplantation and gene editing.

Prominent individuals and organizations, including some scientists working in the field, haveexpressed deep concernsabout the unforeseen consequences that human applications of genetic engineering could have. Some believe there are lines that should not be crossed, especially attempts to create genetically modified human beings (sometimes called designer babies), and suggest that the risks to individuals and to society will never be worth any supposed benefit. Others argue that if its safe, anything goes. A few even hypothesize that humanity will have a moral duty to genetically enhance our children if the technology and underpinning genetics progress.

Using gene editing at the request of health-impacted patients with specific diseases, often referred to as somatic gene therapy, may be acceptable, if it is feasible, proven safe and the patient understands implications of such procedures. But using the same techniques to modify embryos in order to make permanent changes to future generations and to our common genetic heritage thehuman germlineas it is known is far more problematic. It is exceedingly difficult to justify on medical grounds, and carries enormous risks, both for individuals and society. The advent of human germline genetic engineering could lead to the development of new forms of social inequality, discrimination and conflict. Among the risks of heritable genetic modification is the possibility of a modern version of eugenics, with human society being divided into genetic haves and have-nots.

Lack of regulationFriends of the Earth believes that everyone needs to be aware of these new society-changing technologies and be able to engage in decisions about what is safe, ethical and beneficial.

Despite the outstanding environmental, safety and ethical concerns,the synthetic biology marketis expected to reach close to $39 billion by 2020. Already products of synthetic biology, such as synthetic biology-derived vanillin, stevia and oils, are entering food and consumer products ahead of independent environmental and safety assessments, oversight and labeling a worrying precedent for human applications.

Dozens of countries, including those with the most highly developed biotechnology sectors, have explicitly banned heritable human genetic modification, as has the Council of Europes binding 1997 Convention on Human Rights and Biomedicine. However, many countries, including the U.S., have not already enacted such a prohibition.

Friends of the Earth reiterates the call in Principles for the Oversight of Synthetic Biology, signed by 116 civil society groups from around the world, for a prohibition on the use of gene editing and synthetic biology to manipulate the human germline; for safeguards to be implemented to protect public health and the environment from the novel risks of synthetic biology; and open, meaningful and full public participation in decisions regarding its uses. Countries that have not already adopted laws prohibiting the creation of genetically modified human beings, especially including the United States, should do so as soon as possible.

Further information on this topic and recommendations are outlined in the new report Extreme Genetic Engineering and the Human Future.

Gene patentsSynthetic biology techniques and applications for human engineering raise significant questions about intellectual property rights and the ownership of DNA.

About 20 percent of the human genome has already been patented by corporations and scientists, granting companies ownership and sole access to these fundamental building blocks of life. Gene patents are dangerous and unfair: They give corporations monopolies over potentially live-saving research and treatments that are based on pieces of genetic code that have evolved naturally over millenia and are part of our common human heritage.

Scientists are only beginning to understand the complexity of the human genome. Research to date indicates that many common diseases, including cancer, heart disease and Alzheimers, correlate with a combination of environmental and genetic factors.

Patents on genes limit the ability of scientists and health researchers to learn more about gene-to-disease correlations and limit progress in fields that could benefit the health of all people, resulting in increasing prices for tests, impediments to alternative research and barriers to patients access to potentially life-saving technology. As weve seen in the case of patents on two genes that correlate to increased risk for breast cancer and ovarian cancer, gene patents can also prevent patients from receiving second opinions on genetic diagnostic tests.

Friends of the Earth is working to ban the patenting of human genes and all genes that occur naturally on our planet. Our current focus is passing a bill in Congress that would end this practices in the U.S. by reinforcing a fundamental principle of patent law that patents only apply to new, non-obvious products that do not already occur in nature. Decoding genetic material is akin to figuring out the composition of water. Both water and genetic material are common goods that occur naturally. Neither should be patentable.

In a June 2013 decision, the Supreme C
ourt ruled that human genes are may no longer be patented, invalidating the existing patents for over 20 percent of the human genome. Friends of the Earth, represented by the Center for Food Safety, had submitted an amici brief arguing that naturally occurring genes, DNA and cDNA must not be patentable. This marked a huge victory on the issue only apply to new, non-obvious products that do not already occurring in nature.

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Extreme genetic engineering and the human future - Friends ...

New Jersey Medical School – Wikipedia

New Jersey Medical School (NJMS)also known as Rutgers New Jersey Medical Schoolis a graduate medical school of Rutgers University that is part of the division of Biomedical and Health Sciences. NJMS is the oldest school of medicine in New Jersey. The school of medicine was founded in 1954 as the Seton Hall College of Medicine and Dentistry, established under the auspices of the Roman Catholic Archdiocese of Newark, in Jersey City, New Jersey. On August 6, 1954, the College was incorporated as a legal entity separate from Seton Hall University, but with an interlocking Board of Trustees. The first class of 80 students was admitted to the four-year MD program in September 1956, becoming only the sixth medical school in the New York City metropolitan area. In 1965, the institution was acquired by the State of New Jersey, renamed the New Jersey College of Medicine and Dentistry (NJCMD), and relocated to Newark, New Jersey. With the passing of the Medical and Dental Education Act of 1970, signed into law by Governor William T. Cahill on June 16, the College of Medicine and Dentistry of New Jersey (CMDNJ) was created, merging NJCMD with the two-year medical school established at Rutgers University in 1961, under a single board of trustees.

With the creation of the CMDNJ, the medical school adopted its title the New Jersey Medical School. In 1981, legislation signed on December 10 by Governor Byrne established CMDNJ as the University of Medicine and Dentistry of New Jersey (UMDNJ). NJMS served as one of five regional campuses that constitute the UMDNJ health science institution. On June 28, 2012 the New Jersey state legislature passed a bill that dissolved the University of Medicine and Dentistry of New Jersey and merged most of its schools including New Jersey Medical School with Rutgers University forming a new Rutgers Division of Biomedical and Health Sciences effective July 1, 2013. With a cohesive student body, each class consisting of approximately 170 students, NJMS is experiencing impressive growth on a number of fronts. Robert L. Johnson is the current Dean.

In 2004, the school received $104 million in extramural grants supporting basic, clinical and translational research. New Jersey Medical School is also home to the Global Tuberculosis Institute, The Institute for Ophthalmology and Visual Science, and the Center for Emerging and Reemerging Pathogens. New Jersey Medical School is a charter member of the New Jersey Stem Cell Research and Education Foundation. The Summer Student Research Program provides students with stipends to conduct research in the laboratories of NJMS faculty. Each year, more than 100 first- and second-year students, as well as prospective students considering medical school, participate in the program, which has a strong emphasis on cancer research and heart, lung and blood research. NJMS faculty have contributed significantly to medical science breakthroughs including the development of the worldwide standard in knee replacement, the New Jersey Knee; a patented method for the early detection of Lyme disease; the identification of pediatric AIDS and the development of drug-therapy to reduce the likelihood of pre-natal transmission; and proof of the connection between smoking and cancer resulting in the warning message printed on cigarette packages.

New Jersey Medical Schools core teaching hospital, The University Hospital, is located on campus. It is home to a Level I Trauma Center, the busiest in the state, and one of the nations most active liver transplant programs. The 504-bed facility is also highly regarded for its Comprehensive Stroke Center, the New Jersey Cardiovascular Institute (NJCI), the cochlear Implant Program, a neurosurgical intensive care unit and a special Brain Tumor Program, the Neurological Institute of New Jersey, a federally designated spinal cord injury program and The University Center for Bloodless Surgery and Medicine. University Hospital is also the states single largest provider of charity care. Approximately 500 residents are pursuing advanced clinical training at University Hospital in 18 accredited programs.

Other major affiliated teaching sites include Hackensack University Medical Center, Morristown Medical Center, and the East Orange Veterans Affairs Hospital.

Admission to NJMS is highly selective and competitive. NJMS selects its students on the basis of academic excellence, leadership qualities, demonstrated compassion for others and broad extracurricular experiences. One hundred and seventy students enrolled in the class of 2012, selected from over 5,000 applicants. All applicants must be either permanent residents or citizens of the United States, meet specific course requirements, and take the Medical College Admissions Test (MCAT).

Deans of NJMS:

Charles L. Brown, MD (195559)

James E. McCormack, MD (196066)

Arthur J. Lewis, MD (1966)

Desmond Bonnycastle, MD, PhD (acting 1967)

Rulon Rawson, MD (196772)

Harold Kaminetsky, MD (acting dean and dean, 197274)

Stanley S. Bergen, Jr., MD (acting 1974)

Vincent Lanzoni, MD, PhD (197587)

Stuart D. Cook, MD (acting 1987-89)

Ruy V. Loureno, MD (December 1989-June 2000)

Joel A. DeLisa, MD, MS (interim July 2000-December 2000)

Russell T. Joffe, MD (January 2001-September 2005)

Robert L. Johnson, MD (October 2005 to present)

Coordinates: 404421N 741124W / 40.73924N 74.190111W / 40.73924; -74.190111

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New Jersey Medical School - Wikipedia

Molecular nanotechnology – Wikipedia

Molecular nanotechnology (MNT) is a technology based on the ability to build structures to complex, atomic specifications by means of mechanosynthesis.[1] This is distinct from nanoscale materials. Based on Richard Feynman's vision of miniature factories using nanomachines to build complex products (including additional nanomachines), this advanced form of nanotechnology (or molecular manufacturing[2]) would make use of positionally-controlled mechanosynthesis guided by molecular machine systems. MNT would involve combining physical principles demonstrated by biophysics, chemistry, other nanotechnologies, and the molecular machinery of life with the systems engineering principles found in modern macroscale factories.

While conventional chemistry uses inexact processes obtaining inexact results, and biology exploits inexact processes to obtain definitive results, molecular nanotechnology would employ original definitive processes to obtain definitive results. The desire in molecular nanotechnology would be to balance molecular reactions in positionally-controlled locations and orientations to obtain desired chemical reactions, and then to build systems by further assembling the products of these reactions.

A roadmap for the development of MNT is an objective of a broadly based technology project led by Battelle (the manager of several U.S. National Laboratories) and the Foresight Institute.[3] The roadmap was originally scheduled for completion by late 2006, but was released in January 2008.[4] The Nanofactory Collaboration[5] is a more focused ongoing effort involving 23 researchers from 10 organizations and 4 countries that is developing a practical research agenda[6] specifically aimed at positionally-controlled diamond mechanosynthesis and diamondoid nanofactory development. In August 2005, a task force consisting of 50+ international experts from various fields was organized by the Center for Responsible Nanotechnology to study the societal implications of molecular nanotechnology.[7]

One proposed application of MNT is so-called smart materials. This term refers to any sort of material designed and engineered at the nanometer scale for a specific task. It encompasses a wide variety of possible commercial applications. One example would be materials designed to respond differently to various molecules; such a capability could lead, for example, to artificial drugs which would recognize and render inert specific viruses. Another is the idea of self-healing structures, which would repair small tears in a surface naturally in the same way as self-sealing tires or human skin.

A MNT nanosensor would resemble a smart material, involving a small component within a larger machine that would react to its environment and change in some fundamental, intentional way. A very simple example: a photosensor might passively measure the incident light and discharge its absorbed energy as electricity when the light passes above or below a specified threshold, sending a signal to a larger machine. Such a sensor would supposedly cost less and use less power than a conventional sensor, and yet function usefully in all the same applications for example, turning on parking lot lights when it gets dark.

While smart materials and nanosensors both exemplify useful applications of MNT, they pale in comparison with the complexity of the technology most popularly associated with the term: the replicating nanorobot.

MNT nanofacturing is popularly linked with the idea of swarms of coordinated nanoscale robots working together, a popularization of an early proposal by K. Eric Drexler in his 1986 discussions of MNT, but superseded in 1992. In this early proposal, sufficiently capable nanorobots would construct more nanorobots in an artificial environment containing special molecular building blocks.

Critics have doubted both the feasibility of self-replicating nanorobots and the feasibility of control if self-replicating nanorobots could be achieved: they cite the possibility of mutations removing any control and favoring reproduction of mutant pathogenic variations. Advocates address the first doubt by pointing out that the first macroscale autonomous machine replicator, made of Lego blocks, was built and operated experimentally in 2002.[8] While there are sensory advantages present at the macroscale compared to the limited sensorium available at the nanoscale, proposals for positionally controlled nanoscale mechanosynthetic fabrication systems employ dead reckoning of tooltips combined with reliable reaction sequence design to ensure reliable results, hence a limited sensorium is no handicap; similar considerations apply to the positional assembly of small nanoparts. Advocates address the second doubt by arguing that bacteria are (of necessity) evolved to evolve, while nanorobot mutation could be actively prevented by common error-correcting techniques. Similar ideas are advocated in the Foresight Guidelines on Molecular Nanotechnology,[9] and a map of the 137-dimensional replicator design space[10] recently published by Freitas and Merkle provides numerous proposed methods by which replicators could, in principle, be safely controlled by good design.

However, the concept of suppressing mutation raises the question: How can design evolution occur at the nanoscale without a process of random mutation and deterministic selection? Critics argue that MNT advocates have not provided a substitute for such a process of evolution in this nanoscale arena where conventional sensory-based selection processes are lacking. The limits of the sensorium available at the nanoscale could make it difficult or impossible to winnow successes from failures. Advocates argue that design evolution should occur deterministically and strictly under human control, using the conventional engineering paradigm of modeling, design, prototyping, testing, analysis, and redesign.

In any event, since 1992 technical proposals for MNT do not include self-replicating nanorobots, and recent ethical guidelines put forth by MNT advocates prohibit unconstrained self-replication.[9][11]

One of the most important applications of MNT would be medical nanorobotics or nanomedicine, an area pioneered by Robert Freitas in numerous books[12] and papers.[13] The ability to design, build, and deploy large numbers of medical nanorobots would, at a minimum, make possible the rapid elimination of disease and the reliable and relatively painless recovery from physical trauma. Medical nanorobots might also make possible the convenient correction of genetic defects, and help to ensure a greatly expanded lifespan. More controversially, medical nanorobots might be used to augment natural human capabilities. One study has reported on the conditions like tumors, arteriosclerosis, blood clots leading to stroke, accumulation of scar tissue and localized pockets of infection can be possibly be addressed by employing medical nanorobots.[14][15]

Another proposed application of molecular nanotechnology is "utility fog"[16] in which a cloud of networked microscopic robots (simpler than assemblers) would change its shape and properties to form macroscopic objects and tools in accordance with software commands. Rather than modify the current practices of consuming material goods in different forms, utility fog would simply replace many physical objects.

Yet another proposed application of MNT would be phased-array optics (PAO).[17] However, this appears to be a problem addressable by ordinary nanoscale technology. PAO would use the principle of phased-array millimeter technology but at optical wavelengths. This would permit the duplication of any sort of optical effect but virtually. Users could request holograms, sunrises and sunsets, or floating lasers as the mood strikes. PAO systems were described in BC Crandall's Nanotechnology: Molecular Speculations on Global Abundance in the Brian Wowk article "Phased-Array Optics."[18]

Molecular manufacturing is a potential future subfield of nanotechnology that would make it possible to build complex structures at atomic precision.[19] Molecular manufacturing requires significant advances in nanotechnology, but once achieved could produce highly advanced products at low costs and in large quantities in nanofactories weighing a kilogram or more.[19][20] When nanofactories gain the ability to produce other nanofactories production may only be limited by relatively abundant factors such as input materials, energy and software.[20]

The products of molecular manufacturing could range from cheaper, mass-produced versions of known high-tech products to novel products with added capabilities in many areas of application. Some applications that have been suggested are advanced smart materials, nanosensors, medical nanorobots and space travel.[19] Additionally, molecular manufacturing could be used to cheaply produce highly advanced, durable weapons, which is an area of special concern regarding the impact of nanotechnology.[20] Being equipped with compact computers and motors these could be increasingly autonomous and have a large range of capabilities.[20]

According to Chris Phoenix and Mike Treder from the Center for Responsible Nanotechnology as well as Anders Sandberg from the Future of Humanity Institute molecular manufacturing is the application of nanotechnology that poses the most significant global catastrophic risk.[20][21] Several nanotechnology researchers state that the bulk of risk from nanotechnology comes from the potential to lead to war, arms races and destructive global government.[20][21][22] Several reasons have been suggested why the availability of nanotech weaponry may with significant likelihood lead to unstable arms races (compared to e.g. nuclear arms races): (1) A large number of players may be tempted to enter the race since the threshold for doing so is low;[20] (2) the ability to make weapons with molecular manufacturing will be cheap and easy to hide;[20] (3) therefore lack of insight into the other parties' capabilities can tempt players to arm out of caution or to launch preemptive strikes;[20][23] (4) molecular manufacturing may reduce dependency on international trade,[20] a potential peace-promoting factor;[24] (5) wars of aggression may pose a smaller economic threat to the aggressor since manufacturing is cheap and humans may not be needed on the battlefield.[20]

Since self-regulation by all state and non-state actors seems hard to achieve,[25] measures to mitigate war-related risks have mainly been proposed in the area of international cooperation.[20][26] International infrastructure may be expanded giving more sovereignty to the international level. This could help coordinate efforts for arms control.[27] International institutions dedicated specifically to nanotechnology (perhaps analogously to the International Atomic Energy Agency IAEA) or general arms control may also be designed.[26] One may also jointly make differential technological progress on defensive technologies, a policy that players should usually favour.[20] The Center for Responsible Nanotechnology also suggest some technical restrictions.[28] Improved transparency regarding technological capabilities may be another important facilitator for arms-control.[29]

A grey goo is another catastrophic scenario, which was proposed by Eric Drexler in his 1986 book Engines of Creation,[30] has been analyzed by Freitas in "Some Limits to Global Ecophagy by Biovorous Nanoreplicators, with Public Policy Recommendations" [1] and has been a theme in mainstream media and fiction.[31][32] This scenario involves tiny self-replicating robots that consume the entire biosphere using it as a source of energy and building blocks. Nanotech experts including Drexler now discredit the scenario. According to Chris Phoenix a "So-called grey goo could only be the product of a deliberate and difficult engineering process, not an accident".[33] With the advent of nano-biotech, a different scenario called green goo has been forwarded. Here, the malignant substance is not nanobots but rather self-replicating biological organisms engineered through nanotechnology.

Nanotechnology (or molecular nanotechnology to refer more specifically to the goals discussed here) will let us continue the historical trends in manufacturing right up to the fundamental limits imposed by physical law. It will let us make remarkably powerful molecular computers. It will let us make materials over fifty times lighter than steel or aluminium alloy but with the same strength. We'll be able to make jets, rockets, cars or even chairs that, by today's standards, would be remarkably light, strong, and inexpensive. Molecular surgical tools, guided by molecular computers and injected into the blood stream could find and destroy cancer cells or invading bacteria, unclog arteries, or provide oxygen when the circulation is impaired.

Nanotechnology will replace our entire manufacturing base with a new, radically more precise, radically less expensive, and radically more flexible way of making products. The aim is not simply to replace today's computer chip making plants, but also to replace the assembly lines for cars, televisions, telephones, books, surgical tools, missiles, bookcases, airplanes, tractors, and all the rest. The objective is a pervasive change in manufacturing, a change that will leave virtually no product untouched. Economic progress and military readiness in the 21st Century will depend fundamentally on maintaining a competitive position in nanotechnology.

[34]

Despite the current early developmental status of nanotechnology and molecular nanotechnology, much concern surrounds MNT's anticipated impact on economics[35][36] and on law. Whatever the exact effects, MNT, if achieved, would tend to reduce the scarcity of manufactured goods and make many more goods (such as food and health aids) manufacturable.

It is generally considered[by whom?] that future citizens of a molecular-nanotechnological society would still need money, in the form of unforgeable digital cash or physical specie[37] (in special circumstances). They might use such money to buy goods and services that are unique, or limited within the solar system. These might include: matter, energy, information, real estate, design services, entertainment services, legal services, fame, political power, or the attention of other people to one's political/religious/philosophical message. Furthermore, futurists must consider war, even between prosperous states, and non-economic goals.

If MNT were realized, some resources would remain limited, because unique physical objects are limited (a plot of land in the real Jerusalem, mining rights to the larger near-earth asteroids) or because they depend on the goodwill of a particular person (the love of a famous person, a live audience in a musical concert). Demand will always exceed supply for some things, and a political economy may continue to exist in any case. Whether the interest in these limited resources would diminish with the advent of virtual reality, where they could be easily substituted, is yet unclear. One reason why it might not is a hypothetical preference for "the real thing", although such an opinion could easily be mollified if virtual reality were to develop to a certain level of quality.

MNT should make possible nanomedical capabilities able to cure any medical condition not already cured by advances in other areas. Good health would be common, and poor health of any form would be as rare as smallpox and scurvy are today. Even cryonics would be feasible, as cryopreserved tissue could be fully repaired.

Molecular nanotechnology is one of the technologies that some analysts believe could lead to a technological singularity. Some feel that molecular nanotechnology would have daunting risks.[38] It conceivably could enable cheaper and more destructive conventional weapons. Also, molecular nanotechnology might permit weapons of mass destruction that could self-replicate, as viruses and cancer cells do when attacking the human body. Commentators generally agree that, in the event molecular nanotechnology were developed, its self-replication should be permitted only under very controlled or "inherently safe" conditions.

A fear exists that nanomechanical robots, if achieved, and if designed to self-replicate using naturally occurring materials (a difficult task), could consume the entire planet in their hunger for raw materials,[39] or simply crowd out natural life, out-competing it for energy (as happened historically when blue-green algae appeared and outcompeted earlier life forms). Some commentators have referred to this situation as the "grey goo" or "ecophagy" scenario. K. Eric Drexler considers an accidental "grey goo" scenario extremely unlikely and says so in later editions of Engines of Creation.

In light of this perception of potential danger, the Foresight Institute (founded by K. Eric Drexler to prepare for the arrival of future technologies) has drafted a set of guidelines[40] for the ethical development of nanotechnology. These include the banning of free-foraging self-replicating pseudo-organisms on the Earth's surface, at least, and possibly in other places.

The feasibility of the basic technologies analyzed in Nanosystems has been the subject of a formal scientific review by U.S. National Academy of Sciences, and has also been the focus of extensive debate on the internet and in the popular press.

In 2006, U.S. National Academy of Sciences released the report of a study of molecular manufacturing as part of a longer report, A Matter of Size: Triennial Review of the National Nanotechnology Initiative[41] The study committee reviewed the technical content of Nanosystems, and in its conclusion states that no current theoretical analysis can be considered definitive regarding several questions of potential system performance, and that optimal paths for implementing high-performance systems cannot be predicted with confidence. It recommends experimental research to advance knowledge in this area:

A section heading in Drexler's Engines of Creation reads[42] "Universal Assemblers", and the following text speaks of multiple types of assemblers which, collectively, could hypothetically "build almost anything that the laws of nature allow to exist." Drexler's colleague Ralph Merkle has noted that, contrary to widespread legend,[43] Drexler never claimed that assembler systems could build absolutely any molecular structure. The endnotes in Drexler's book explain the qualification "almost": "For example, a delicate structure might be designed that, like a stone arch, would self-destruct unless all its pieces were already in place. If there were no room in the design for the placement and removal of a scaffolding, then the structure might be impossible to build. Few structures of practical interest seem likely to exhibit such a problem, however."

In 1992, Drexler published Nanosystems: Molecular Machinery, Manufacturing, and Computation,[44] a detailed proposal for synthesizing stiff covalent structures using a table-top factory. Diamondoid structures and other stiff covalent structures, if achieved, would have a wide range of possible applications, going far beyond current MEMS technology. An outline of a path was put forward in 1992 for building a table-top factory in the absence of an assembler. Other researchers have begun advancing tentative, alternative proposed paths [5] for this in the years since Nanosystems was published.

In 2004 Richard Jones wrote Soft Machines (nanotechnology and life), a book for lay audiences published by Oxford University. In this book he describes radical nanotechnology (as advocated by Drexler) as a deterministic/mechanistic idea of nano engineered machines that does not take into account the nanoscale challenges such as wetness, stickness, Brownian motion, and high viscosity. He also explains what is soft nanotechnology or more appropriatelly biomimetic nanotechnology which is the way forward, if not the best way, to design functional nanodevices that can cope with all the problems at a nanoscale. One can think of soft nanotechnology as the development of nanomachines that uses the lessons learned from biology on how things work, chemistry to precisely engineer such devices and stochastic physics to model the system and its natural processes in detail.

Several researchers, including Nobel Prize winner Dr. Richard Smalley (19432005),[45] attacked the notion of universal assemblers, leading to a rebuttal from Drexler and colleagues,[46] and eventually to an exchange of letters.[47] Smalley argued that chemistry is extremely complicated, reactions are hard to control, and that a universal assembler is science fiction. Drexler and colleagues, however, noted that Drexler never proposed universal assemblers able to make absolutely anything, but instead proposed more limited assemblers able to make a very wide variety of things. They challenged the relevance of Smalley's arguments to the more specific proposals advanced in Nanosystems. Also, Smalley argued that nearly all of modern chemistry involves reactions that take place in a solvent (usually water), because the small molecules of a solvent contribute many things, such as lowering binding energies for transition states. Since nearly all known chemistry requires a solvent, Smalley felt that Drexler's proposal to use a high vacuum environment was not feasible. However, Drexler addresses this in Nanosystems by showing mathematically that well designed catalysts can provide the effects of a solvent and can fundamentally be made even more efficient than a solvent/enzyme reaction could ever be. It is noteworthy that, contrary to Smalley's opinion that enzymes require water, "Not only do enzymes work vigorously in anhydrous organic media, but in this unnatural milieu they acquire remarkable properties such as greatly enhanced stability, radically altered substrate and enantiomeric specificities, molecular memory, and the ability to catalyse unusual reactions."[48]

For the future, some means have to be found for MNT design evolution at the nanoscale which mimics the process of biological evolution at the molecular scale. Biological evolution proceeds by random variation in ensemble averages of organisms combined with culling of the less-successful variants and reproduction of the more-successful variants, and macroscale engineering design also proceeds by a process of design evolution from simplicity to complexity as set forth somewhat satirically by John Gall: "A complex system that works is invariably found to have evolved from a simple system that worked. . . . A complex system designed from scratch never works and can not be patched up to make it work. You have to start over, beginning with a system that works." [49] A breakthrough in MNT is needed which proceeds from the simple atomic ensembles which can be built with, e.g., an STM to complex MNT systems via a process of design evolution. A handicap in this process is the difficulty of seeing and manipulation at the nanoscale compared to the macroscale which makes deterministic selection of successful trials difficult; in contrast biological evolution proceeds via action of what Richard Dawkins has called the "blind watchmaker" [50] comprising random molecular variation and deterministic reproduction/extinction.

At present in 2007 the practice of nanotechnology embraces both stochastic approaches (in which, for example, supramolecular chemistry creates waterproof pants) and deterministic approaches wherein single molecules (created by stochastic chemistry) are manipulated on substrate surfaces (created by stochastic deposition methods) by deterministic methods comprising nudging them with STM or AFM probes and causing simple binding or cleavage reactions to occur. The dream of a complex, deterministic molecular nanotechnology remains elusive. Since the mid-1990s, thousands of surface scientists and thin film technocrats have latched on to the nanotechnology bandwagon and redefined their disciplines as nanotechnology. This has caused much confusion in the field and has spawned thousands of "nano"-papers on the peer reviewed literature. Most of these reports are extensions of the more ordinary research done in the parent fields.

The feasibility of Drexler's proposals largely depends, therefore, on whether designs like those in Nanosystems could be built in the absence of a universal assembler to build them and would work as described. Supporters of molecular nanotechnology frequently claim that no significant errors have been discovered in Nanosystems since 1992. Even some critics concede[51] that "Drexler has carefully considered a number of physical principles underlying the 'high level' aspects of the nanosystems he proposes and, indeed, has thought in some detail" about some issues.

Other critics claim, however, that Nanosystems omits important chemical details about the low-level 'machine language' of molecular nanotechnology.[52][53][54][55] They also claim that much of the other low-level chemistry in Nanosystems requires extensive further work, and that Drexler's higher-level designs therefore rest on speculative foundations. Recent such further work by Freitas and Merkle [56] is aimed at strengthening these foundations by filling the existing gaps in the low-level chemistry.

Drexler argues that we may need to wait until our conventional nanotechnology improves before solving these issues: "Molecular manufacturing will result from a series of advances in molecular machine systems, much as the first Moon landing resulted from a series of advances in liquid-fuel rocket systems. We are now in a position like that of the British Interplanetary Society of the 1930s which described how multistage liquid-fueled rockets could reach the Moon and pointed to early rockets as illustrations of the basic principle."[57] However, Freitas and Merkle argue [58] that a focused effort to achieve diamond mechanosynthesis (DMS) can begin now, using existing technology, and might achieve success in less than a decade if their "direct-to-DMS approach is pursued rather than a more circuitous development approach that seeks to implement less efficacious nondiamondoid molecular manufacturing technologies before progressing to diamondoid".

To summarize the arguments against feasibility: First, critics argue that a primary barrier to achieving molecular nanotechnology is the lack of an efficient way to create machines on a molecular/atomic scale, especially in the absence of a well-defined path toward a self-replicating assembler or diamondoid nanofactory. Advocates respond that a preliminary research path leading to a diamondoid nanofactory is being developed.[6]

A second difficulty in reaching molecular nanotechnology is design. Hand design of a gear or bearing at the level of atoms might take a few to several weeks. While Drexler, Merkle and others have created designs of simple parts, no comprehensive design effort for anything approaching the complexity of a Model T Ford has been attempted. Advocates respond that it is difficult to undertake a comprehensive design effort in the absence of significant funding for such efforts, and that despite this handicap much useful design-ahead has nevertheless been accomplished with new software tools that have been developed, e.g., at Nanorex.[59]

In the latest report A Matter of Size: Triennial Review of the National Nanotechnology Initiative[41] put out by the National Academies Press in December 2006 (roughly twenty years after Engines of Creation was published), no clear way forward toward molecular nanotechnology could yet be seen, as per the conclusion on page 108 of that report: "Although theoretical calculations can be made today, the eventually attainable range of chemical reaction cycles, error rates, speed of operation, and thermodynamic efficiencies of such bottom-up manufacturing systems cannot be reliably predicted at this time. Thus, the eventually attainable perfection and complexity of manufactured products, while they can be calculated in theory, cannot be predicted with confidence. Finally, the optimum research paths that might lead to systems which greatly exceed the thermodynamic efficiencies and other capabilities of biological systems cannot be reliably predicted at this time. Research funding that is based on the ability of investigators to produce experimental demonstrations that link to abstract models and guide long-term vision is most appropriate to achieve this goal." This call for research leading to demonstrations is welcomed by groups such as the Nanofactory Collaboration who are specifically seeking experimental successes in diamond mechanosynthesis.[60] The "Technology Roadmap for Productive Nanosystems"[61] aims to offer additional constructive insights.

It is perhaps interesting to ask whether or not most structures consistent with physical law can in fact be manufactured. Advocates assert that to achieve most of the vision of molecular manufacturing it is not necessary to be able to build "any structure that is compatible with natural law." Rather, it is necessary to be able to build only a sufficient (possibly modest) subset of such structuresas is true, in fact, of any practical manufacturing process used in the world today, and is true even in biology. In any event, as Richard Feynman once said, "It is scientific only to say what's more likely or less likely, and not to be proving all the time what's possible or impossible."[62]

There is a growing body of peer-reviewed theoretical work on synthesizing diamond by mechanically removing/adding hydrogen atoms [63] and depositing carbon atoms [64][65][66][67][68][69] (a process known as mechanosynthesis). This work is slowly permeating the broader nanoscience community and is being critiqued. For instance, Peng et al. (2006)[70] (in the continuing research effort by Freitas, Merkle and their collaborators) reports that the most-studied mechanosynthesis tooltip motif (DCB6Ge) successfully places a C2 carbon dimer on a C(110) diamond surface at both 300K (room temperature) and 80K (liquid nitrogen temperature), and that the silicon variant (DCB6Si) also works at 80K but not at 300K. Over 100,000 CPU hours were invested in this latest study. The DCB6 tooltip motif, initially described by Merkle and Freitas at a Foresight Conference in 2002, was the first complete tooltip ever proposed for diamond mechanosynthesis and remains the only tooltip motif that has been successfully simulated for its intended function on a full 200-atom diamond surface.

The tooltips modeled in this work are intended to be used only in carefully controlled environments (e.g., vacuum). Maximum acceptable limits for tooltip translational and rotational misplacement errors are reported in Peng et al. (2006) -- tooltips must be positioned with great accuracy to avoid bonding the dimer incorrectly. Peng et al. (2006) reports that increasing the handle thickness from 4 support planes of C atoms above the tooltip to 5 planes decreases the resonance frequency of the entire structure from 2.0THz to 1.8THz. More importantly, the vibrational footprints of a DCB6Ge tooltip mounted on a 384-atom handle and of the same tooltip mounted on a similarly constrained but much larger 636-atom "crossbar" handle are virtually identical in the non-crossbar directions. Additional computational studies modeling still bigger handle structures are welcome, but the ability to precisely position SPM tips to the requisite atomic accuracy has been repeatedly demonstrated experimentally at low temperature,[71][72] or even at room temperature[73][74] constituting a basic existence proof for this capability.

Further research[75] to consider additional tooltips will require time-consuming computational chemistry and difficult laboratory work.

A working nanofactory would require a variety of well-designed tips for different reactions, and detailed analyses of placing atoms on more complicated surfaces. Although this appears a challenging problem given current resources, many tools will be available to help future researchers: Moore's Law predicts further increases in computer power, semiconductor fabrication techniques continue to approach the nanoscale, and researchers grow ever more skilled at using proteins, ribosomes and DNA to perform novel chemistry.

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Molecular nanotechnology - Wikipedia

Resveratrol – Wikipedia

ResveratrolChemical structures of cis- ((Z)-resveratrol, left) and trans-resveratrol ((E)-resveratrol, right)[1]NamesOther names

trans-3,5,4-Trihydroxystilbene;3,4,5-Stilbenetriol;trans-Resveratrol;(E)-5-(p-Hydroxystyryl)resorcinol;(E)-5-(4-hydroxystyryl)benzene-1,3-diol

Oc2ccc(C=Cc1cc(O)cc(O)c1)cc2

Resveratrol (3,5,4-trihydroxy-trans-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or, when the plant is under attack by pathogens such as bacteria or fungi.[5][6] Sources of resveratrol in food include the skin of grapes, blueberries, raspberries, mulberries.[7]

Although it is used as a dietary supplement, there is no good evidence that consuming resveratrol affects life expectancy or human health.[8][9]

There is no evidence of benefit from resveratrol in those who already have heart disease.[10] A 2014 Chinese meta-analysis found weak evidence that high-dose resveratrol supplementation could reduce systolic blood pressure.[11]

As of 2016[update], there is no evidence of an effect of resveratrol on cancer in humans.[12]

There is no conclusive human evidence for an effect of resveratrol on metabolism.[13][14]

There is no evidence for an effect of resveratrol on lifespan in humans as of 2011[update].[15]

In 2010, GlaxoSmithKline suspended a small clinical trial of SRT501, a proprietary form of resveratrol, due to safety concerns, and terminated the study later that year. SRT501 was composed of microparticles (< 5 m) intended to enhance absorption and was delivered at a dose 5 grams per day, causing gastrointestinal disorders and diarrhea in many subjects.[16] Although limited human studies have shown resveratrol is well-tolerated,[11][14] one clinical study of Alzheimer's disease patients showed there were side effects from daily intake of up to 2 grams, including nausea, diarrhea, and weight loss.[17]

Although in vitro studies indicate resveratrol activates sirtuin 1[18] and PGC-1, and affects functioning of mitochondria,[19] other research disputes this effect.[20][21]

In cells treated with resveratrol, an increase is observed in the action of MnSOD (SOD2)[22] and in GPER activity.[23]

One way of administering resveratrol in humans may be buccal delivery, that is without swallowing, by direct absorption through tissues on the inside of the mouth. When one milligram of resveratrol in 50 ml 50% alcohol/ water solution was retained in the mouth for one minute before swallowing, 37ng/ml of free resveratrol was measured in plasma two minutes later. This level of unchanged resveratrol in blood can only be achieved with 250mg of resveratrol taken in a pill form.[24] However, the viability of a buccal delivery method is called into question due to the low aqueous solubility of the molecule. For a drug to be absorbed transmucosally it must be in free-form or dissolved.[25][26] Resveratrol fits the criteria for oral transmucosal dosing, except for this caveat. The low aqueous solubility greatly limits the amount that can be absorbed through the buccal mucosa. Resveratrol that is attempted to be taken buccally was expected to pass through the mucous membrane of the mouth and be absorbed as an oral dose,[27] however, the need to explore buccal delivery in future pharmaceutical formulations was expressed.[26][28]

While 70% of orally administered resveratrol is absorbed, its oral bioavailability is approximately 0.5% due to extensive hepatic glucuronidation and sulfation.[29] Resveratrol given in a proprietary formulation SRT-501 (3 or 5 g), developed by Sirtris Pharmaceuticals, reached five to eight times higher blood levels. These levels did approach the concentration necessary to exert the effects shown in animal models and in vitro experiments.[30]

In rats, less than 5% of the oral dose was observed as free resveratrol in blood plasma.[31] There is a hypothesis that resveratrol from wine could have higher bioavailability than resveratrol from a pill.[32]

In a human study involving oral administration of 500mg over 13 weeks, resveratrol was detected in cerebrospinal fluid, indicating that it had crossed the blood-brain barrier.[17]

Resveratrol gets extensively metabolized in the body, with the liver and lungs as the major sites of its metabolism.[33]

Resveratrol (3,5,4'-trihydroxystilbene) is a stilbenoid, a derivative of stilbene.

It exists as two geometric isomers: cis- (Z) and trans- (E), with the trans-isomer shown in the top image. The trans- and cis-resveratrol can be either free or bound to glucose.[34]

The trans- form can undergo isomerization to the cis- form when exposed to ultraviolet irradiation,[35] a process called photoisomerization:[36]

One study showed that ultraviolet irradiation to cis-resveratrol induces further photochemical reaction, producing a fluorescent molecule named "Resveratrone".[37]

Trans-resveratrol in the powder form was found to be stable under "accelerated stability" conditions of 75% humidity and 40C in the presence of air.[38] The trans isomer is also stabilized by the presence of transport proteins.[39] Resveratrol content also was stable in the skins of grapes and pomace taken after fermentation and stored for a long period.[40]lH- and 13C-NMR data for the four most common forms of resveratrols are reported in literature.[34]

Resveratrol is produced in plants by the action of the enzyme, resveratrol synthase.[41]

The grapevine fungal pathogen Botrytis cinerea is able to oxidise resveratrol into metabolites showing attenuated antifungal activities. Those include the resveratrol dimers restrytisol A, B, and C, resveratrol trans-dehydrodimer, leachinol F, and pallidol.[42] The soil bacterium Bacillus cereus can be used to transform resveratrol into piceid (resveratrol 3-O-beta-D-glucoside).[43]

Resveratrol is a phytoalexin, a class of compounds produced by many plants when they are infected by pathogens or physically harmed by cutting, crushing, or ultraviolet radiation.[44]

Plants that synthesize resveratrol include knotweeds, pine trees including Scots pine and Eastern white pine, grape vines, peanut plants, cocoa bushes, and Vaccinium shrubs that produce berries, including blueberries, raspberries, mulberries, cranberries, and bilberries.[5][7][44]

The levels of resveratrol found in food varies considerably, even in the same food from season to season and batch to batch.[5]

In a 2007 review of published resveratrol concentrations, the average in red wines is 69941899999999999991.91.7mg trans-resveratrol/L (70008199999999999998.27.5M, ranging from nondetectable levels to 14.3mg/l (62.7M) trans-resveratrol. Levels of cis-resveratrol follow the same trend as trans-resveratrol.[46]

In general, wines made from grapes of the Pinot Noir and St. Laurent varieties showed the highest level of trans-resveratrol, though no wine or region can yet be said to produce wines with significantly higher concentrations than any other wine or region.[46]Champagne and vinegar also contain appreciable levels of resveratrol.[45]

Red wine contains between 0.2 and 5.8mg/l, depending on the grape variety. White wine has much less because red wine is fermented with the skins, allowing the wine to extract the resveratrol, whereas white wine is fermented after the skin has been removed.[5] The composition of wine is different from that of grapes since the extraction of resveratrol from grapes depends on the duration of the skin contact, and the resveratrol 3-glucosides are in part hydrolysed, yielding both trans- and cis-resveratrol.[5]

Ounce for ounce, peanuts have about 25% as much resveratrol as red wine.[5]Peanuts, especially sprouted peanuts, have a content similar to grapes in a range of 2.3 to 4.5g/g before sprouting, and after sprouting, in a range of 11.7 to 25.7g/g, depending upon peanut cultivar.[44][45]

Mulberries (especially the skin) are a source of as much as 50 micrograms of resveratrol per gram dry weight.[47]

There are no studies to show that resveratrol supplements are beneficial in humans.[48][49][50] Sales of resveratrol supplements increased in 2006 after studies on non-humans.[48]

Harvard University scientist and professor David Sinclair co-founded Sirtris Pharmaceuticals, the initial product of which was a resveratrol formulation;[51] Sinclair became known for making statements about resveratrol like: (It's) as close to a miraculous molecule as you can find.... One hundred years from now, people will maybe be taking these molecules on a daily basis to prevent heart disease, stroke, and cancer.[52] Most of the anti-aging field was more cautious, especially with regard to what else resveratrol might do in the body and its lack of bioavailability.[52][53]

Sinclair and others obtained significant news coverage about resveratrol.[54][55] Sinclair is often quoted and pictured in online ads for resveratrol supplements, many of which implied endorsement of the advertised product even though Sinclair had not endorsed them.[56]

Supplements vary in purity and can contain anywhere from 50 percent to 99 percent resveratrol.[citation needed]

The first mention of resveratrol was in a Japanese article in 1939 by Michio Takaoka, who isolated it from Veratrum album, variety grandiflorum, and later, in 1963, from the roots of Japanese knotweed.[44][57][58][59]

A 2011 systematic review of existing resveratrol research demonstrated there was not enough evidence to demonstrate its effect on longevity or human diseases, nor could there be recommendations for intake beyond the amount normally obtained through dietary sources, estimated as being less than 4 mg/day.[8] Much of the research showing positive effects has been done on animals, with insufficient clinical research on humans.[8] Resveratrol research in animals and humans remains active.[60][61]

As of 2014[update], the results of studies on laboratory animals or human clinical trials concerning the effects of resveratrol on cancer are inconsistent,[12] even if massive doses of resveratrol are used.[62]

A preliminary, one-year clinical trial of subjects with Alzheimer's disease showed that consuming 2 grams of resveratrol daily was well-tolerated and reduced some disease biomarkers in cerebrospinal fluid and blood, although other biomarkers and progressive dementia were unaffected.[17] Other preliminary human studies indicated that short-term ingestion of resveratrol increased cerebral blood flow in normal subjects[63] and in people with diabetes.[64] Resveratrol is under study for its potential to limit secondary damage after ischemic stroke or acute brain trauma.[65]

Although moderate drinking of red wine is generally associated with reduced risk of heart disease,[66] an association known as "the French paradox",[67] there is little evidence that resveratrol in red wine may have a role in this possible effect.[68]

Animal studies are being conducted to discern potential metabolic and antidiabetic effects of resveratrol.[69] In vitro, resveratrol was shown to act as an agonist of Peroxisome proliferator-activated receptor gamma, a nuclear receptor under pharmacological research as a potential treatment for type 2 diabetes.[70] Although one systematic review and meta-analysis noted that resveratrol is a "leading candidate" compound for serving as an adjunct pharmacotherapy for type 2 diabetes,[71] there is little evidence for its use as a possible treatment for diabetes.[69]

Despite considerable in vitro and animal research, there is no evidence that resveratrol taken orally or topically has any effect on human skin.[72] Preliminary studies have been conducted on resveratrol to understand its potential as a therapy for melanoma.[73][74]

Original post:

Resveratrol - Wikipedia

Resveratrol | Which Works Best | Facts About Side Effects

What Is Resveratrol?

It is a compound found naturally in foods such as grapes, nuts, red wine, peanuts, some berries, and possibly in other fruits and plants. As a result of the large amount of publicity about the French Paradox Study discussed on the website, researchers investigating the potential positive effects of red wine consumption eventually focused on resveratrol, one of the substances found in red wine. Other studies followed and the research continues today

Click Here To See The #1 Top Rated Best Value Resveratrol

Selecting the highest quality supplement is not easy. The science and research is exciting, but new. There has been some excellent work done by many researchers on the potential health benefits, and we have included a number of videos on this site in unedited form and in full for you to examine. Its very impressive stuff, but we let the real experts do the talking. So, we dont extrapolate their views and delve into hype like you will see on most of the other websites. Please view those videos right here on this website. They are loaded with unbiased, non-commercial information from scientists, researchers and experts.

If you decide that supplementation is right for you, then the problem becomes choosing the best supplement. Thats not so easy and we hope to help.

Click Here To See The #1 Top Rated Best Value Resveratrol

Check out the page titled Resveratrol Benefits and watch the highly informative story on 60 Minutes on this website, as well as the in-depth interviews of pioneering-researcher, David Sinclair on The Charlie Rose Show. Its all here for you too see and examine for yourself, without any hype from us. There are also many links to prominent news stories in the most respected news outlets and organizations, such as the NIH (National Institute of Health). You will find many links to important resveratrol articles from leading publications and leading resources listed here, all in one place for your convenience.

This is all very exciting and impressive but once you have decided whether or not to use supplements containing this substance, there is still the problem of choosing the right supplement.

Avoid supplement products which are made from low-purity trans-resveratrol, because they contain unacceptably high amounts of Emodin. Emodin can act as a laxative and cause stomach cramps and intestinal distress. Read more about it on this website.

Avoid products that contain additional ingredients such as additives, fillers, or other substances.

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Is this unique compound the anti aging secret to controlling the aging process? Can a person in their 80s move and feel like a person in their 50s? Studies have shown that this molecule has offset the effects of high caloric intake in mice and extended their longevity. Will the same effect take place in humans? Can resveratrol supplements prevent diseases associated with aging? Are anti aging and reduced incidence of disease realistic benefits of this substance? Does it help with weight loss? Watch the videos on this website with noted scientists and science writers and hear the facts from them about where the research stands now.

In Vino Sanitus in wine there is health

There was a report some years ago on the TV program 60 Minutes about a study that examined what is known as the French Paradox Study. The French Paradox Study demonstrated that the folks in France were less likely to die from heart disease even though they consumed high fat diets. It was noted in the study that the French consumed large amounts of red wine and the theory developed that the red wine somehow protected the hearts of the wine drinking French people.

Numerous other studies followed and the substance attracted much scientific interest as the possible compound in red wine that may be an important factor in the positive heart healthy effects.

REFERENCES

Wikipediahttps://en.wikipedia.org/wiki/Resveratrol Clinical Trialshttps://clinicaltrials.gov/search/intervention=RESVERATROLNew York Times Topicshttps://www.nytimes.com/topic/subject/resveratrol

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Resveratrol | Which Works Best | Facts About Side Effects

The Threat of Human Genetic Engineering – hgalert.org

David King

The main debate around human genetics currently centres on theethics of genetic testing, and possibilities for geneticdiscrimination and selective eugenics. But while ethicists andthe media constantly re-hash these issues, a small group ofscientists and publicists are working towards an even morefrightening prospect: the intentional genetic engineering ofhuman beings. Just as Ian Wilmut presented us with the firstclone of an adult mammal, Dolly, as a fait accompli, so thesescientists aim to set in place the tools of a newtechno-eugenics, before the public has ever had a chance todecide whether this is the direction we want to go in. Thepublicists, meanwhile are trying to convince us that thesedevelopments are inevitable. The Campaign Against Human GeneticEngineering, has been set up in response to this threat.

Currently, genetic engineering is only applied tonon-reproductive cells (this is known as 'gene therapy') in orderto treat diseases in a single patient, rather than in all theirdescendants. Gene therapy is still very unsuccessful, and we areoften told that the prospect of reproductive genetic engineeringis remote. In fact, the basic technologies for human geneticengineering (HGE) have been available for some time and atpresent are being refined and improved in a number of ways. Weshould not make the same mistake that was made with cloning, andassume that the issue is one for the far future.

In the first instance, the likely justifications of HGE willbe medical. One major step towards reproductive geneticengineering is the proposal by US gene therapy pioneer, FrenchAnderson, to begin doing gene therapy on foetuses, to treatcertain genetic diseases. Although not directly targeted atreproductive cells, Anderson's proposed technique poses arelatively high risk that genes will be 'inadvertently' alteredin the reproductive cells of the foetus, as well as in the bloodcells which he wants to fix. Thus, if he is allowed to go ahead,the descendants of the foetus will be genetically engineered inevery cell of their body. Another scientist, James Grifo of NewYork University is transferring cell nuclei from the eggs ofolder to younger women, using similar techniques to those used incloning. He aims to overcome certain fertility problems, but theresult would be babies with three genetic parents, arguably aform of HGE. In addition to the two normal parents, these babieswill have mitochondria (gene-containing subcellular bodies whichcontrol energy production in cells) from the younger woman.

Anderson is a declared advocate of HGE for medical purposes,and was a speaker at a symposium last year at UCLA, at whichadvocates of HGE set out their stall. At the symposium, which wasattended by nearly 1,000 people, James Watson, of DNA discoveryfame, advocated the use of HGE not merely for medical purposes,but for 'enhancement': 'And the other thing, because no onereally has the guts to say it, I mean, if we could make betterhuman beings by knowing how to add genes, why shouldn't we doit?'

In his recent book, Re-Making Eden (1998), Princetonbiologist, Lee Silver celebrates the coming future of human'enhancement', in which the health, appearance, personality,cognitive ability, sensory capacity, and life-span of ourchildren all become artifacts of genetic engineering, literallyselected from a catalog. Silver acknowledges that the costs ofthese technologies will limit their full use to only a small'elite', so that over time society will segregate into the"GenRich" and the "Naturals":

"The GenRich - who account for 10 percent of the Americanpopulation - all carry synthetic genes... that were created inthe laboratory ...All aspects of the economy, the media, theentertainment industry, and the knowledge industry are controlledby members of the GenRich class...Naturals work as low-paidservice providers or as labourers, and their children go topublic schools... If the accumulation of genetic knowledge andadvances in genetic enhancement technology continue ... theGenRich class and the Natural class will become...entirelyseparate species with no ability to cross-breed, and with as muchromantic interest in each other as a current human would have fora chimpanzee."

Silver, another speaker at the UCLA symposium, believes thatthese trends should not and cannot be stopped, because to do sowould infringe on liberty.

Most scientists say that what is preventing them fromembarking on HGE is the risk that the process will itselfgenerate new mutations, which will be passed on to futuregenerations. Official scientific and ethical bodies tend to relyon this as the basis for forbidding attempts at HGE, rather thanany principled opposition to the idea.

In my view, we should not allow ourselves to be lulled into afalse sense of security by this argument. Experience withgenetically engineered crops, for example, shows that we areunlikely ever to arrive at a situation when we can be sure thatthe risks are zero. Instead, when scientists are ready toproceed, we will be told that the risks are 'acceptable',compared to the benefits. Meanwhile, there will be people tellingus loudly that since they are taking the risks with theirchildren, we have no right to interfere.

One of the flaws in the argument of those who support thepossibility of HGE for medical purposes is that there seem to bevery few good examples where it is the only solution to themedical problem of genetic disease. The main advantage of HGE issaid to be the elimination of disease genes from a family. Yet innearly all cases, existing technologies of prenatal andpreimplantation genetic testing of embryos allow the avoidance ofactual disease. There are only a few very rare cases where HGE isthe only option.

Furthermore, there is always another solution for thosecouples who are certain to produce a genetically disabled childand cannot, or do not want to deal with this possibility. Theycan choose not to have children, to adopt a child, or to usedonor eggs or sperm. Parenthood is not the only way to createfulfilment through close, intimate and long lasting relationshipswith children. The question we have to ask is whether we shoulddevelop the technology for HGE, in order to satisfy a very smallnumber of people.

Although the arguments for the first uses of HGE will bemedical, in fact the main market for the technology will be'enhancement'. Once it was available, how would it be possible toensure that HGE was used for purely medical purposes? The sameproblem applies to prenatal genetic screening and to somatic genetherapy, and not only are there no accepted criteria for decidingwhat constitutes a medical condition, but in a free marketsociety there seems to be no convincing mechanism for arriving atsuch decision. The best answer that conventional medical ethicsseems to have is to `leave it up to the parents', ie. to marketforces.

Existing trends leave little doubt about what to expect.Sophisticated medical technology and medical personnel arealready employed in increasingly fashionable cosmetic surgery.Another example is the use of genetically engineered human growthhormone (HGH), developed to remedy the medical condition ofgrowth hormone deficiency. Because of aggressive marketing by itsmanufacturers, HGH is routinely prescribed in the USA to normalshort children with no hormone deficiency. If these pressuresalready exist, how much stronger will they be for a technologywith as great a power to manipulate human life as HGE?

Germ line manipulation opens up, for the first time in humanhistory, the possibility of consciously designing human beings,in a myriad of different ways. I am not generally happy aboutusing the concept of playing God, but it is difficult to avoid inthis case. The advocates of genetic engineering point out thathumans constantly 'play God', in a sense, by interfering withnature. Yet the environmental crisis has forced us to realisethat many of the ways we already do this are not wise, destroythe environment and cannot be sustained. Furthermore, HGE is notjust a continuation of
existing trends. Once we begin toconsciously design ourselves, we will have entered a completelynew era of human history, in which human subjects, rather thanbeing accepted as they are will become just another kind ofobject, shaped according to parental whims and market forces.

In essence, the vision of the advocates of HGE is a sanitisedversion of the old eugenics doctrines, updated for the 1990s.Instead of 'elimination of the unfit', HGE is presented as a toolto end, once and for all, the suffering associated with geneticdiseases. And in place of 'improving the race', the 1990semphasis is on freedom of choice, where 'reproductive rights'become consumer rights to choose the characteristics of yourchild. No doubt the resulting eugenic society would be a littleless brutal than those of earlier this century. On the other handthe capabilities of geneticists are much greater now than theywere then. Unrestrained, HGE is perfectly capable of producingLee Silver's dystopia.

In most cases, the public's function with respect to scienceis to consume its products, or to pay to clean up the mess. Butwith HGE, there is still time to prevent it, before it becomesreality. We need an international ban on HGE and cloning. Thereis a good chance this can be achieved, since both are alreadyillegal in many countries. Of course it may be impossible toprevent a scientist, somewhere, from attempting to clone orgenetically engineer humans. But there is a great differencebetween a society which would jail such a scientist and one whichwould permit HGE to become widespread and respectable. If we failto act now, we will only have ourselves to blame.

Read more:
The Threat of Human Genetic Engineering - hgalert.org

Ode: Intimations of Immortality – Wikipedia

Ode: Intimations of Immortality from Recollections of Early Childhood (also known as Ode, Immortality Ode or Great Ode) is a poem by William Wordsworth, completed in 1804 and published in Poems, in Two Volumes (1807). The poem was completed in two parts, with the first four stanzas written among a series of poems composed in 1802 about childhood. The first part of the poem was completed on 27 March 1802 and a copy was provided to Wordsworth's friend and fellow poet, Samuel Taylor Coleridge, who responded with his own poem, Dejection: An Ode, in April. The fourth stanza of the ode ends with a question, and Wordsworth was finally able to answer it with 7 additional stanzas completed in early 1804. It was first printed as Ode in 1807, and it was not until 1815 that it was edited and reworked to the version that is currently known, Ode: Intimations of Immortality.

The poem is an irregular Pindaric ode in 11 stanzas that combines aspects of Coleridge's Conversation poems, the religious sentiments of the Bible and the works of Saint Augustine, and aspects of the elegiac and apocalyptic traditions. It is split into three movements: the first four stanzas discuss death, and the loss of youth and innocence; the second four stanzas describes how age causes man to lose sight of the divine, and the final three stanzas express hope that the memory of the divine allow us to sympathise with our fellow man. The poem relies on the concept of Pre-existence, the idea that the soul existed before the body, to connect children with the ability to witness the divine within nature. As children mature, they become more worldly and lose this divine vision, and the ode reveals Wordsworth's understanding of psychological development that is also found in his poems The Prelude and Tintern Abbey. Wordsworth's praise of the child as the "best philosopher" was criticised by Coleridge and became the source of later critical discussion.

Modern critics sometimes have referred to Wordsworth's poem as the "Great Ode"[1][2] and ranked it among his best poems,[3] but this wasn't always the case. Contemporary reviews of the poem were mixed, with many reviewers attacking the work or, like Lord Byron, dismissing the work without analysis. The critics felt that Wordsworth's subject matter was too "low" and some felt that the emphasis on childhood was misplaced. Among the Romantic poets, most praised various aspects of the poem however. By the Victorian period, most reviews of the ode were positive with only John Ruskin taking a strong negative stance against the poem. The poem continued to be well received into the 20th-century, with few exceptions. The majority ranked it as one of Wordsworth's greatest poems.

In 1802, Wordsworth wrote many poems that dealt with his youth. These poems were partly inspired by his conversations with his sister, Dorothy, whom he was living with in the Lake District at the time. The poems, beginning with The Butterfly and ending with To the Cuckoo, were all based on Wordsworth's recalling both the sensory and emotional experience of his childhood. From To the Cuckoo, he moved onto The Rainbow, both written on 26 March 1802, and then on to Ode: Intimation of Immortality from Recollections of Early Childhood. As he moved from poem to poem, he began to question why, as a child, he once was able to see an immortal presence within nature but as an adult that was fading away except in the few moments he was able to meditate on experiences found in poems like To the Cuckoo. While sitting at breakfast on 27 March, he began to compose the ode. He was able to write four stanzas that put forth the question about the faded image and ended, "Where is it now, the glory and the dream?" The poem would remain in its smaller, four-stanza version until 1804.[5]

The short version of the ode was possibly finished in one day because Wordsworth left the next day to spend time with Samuel Taylor Coleridge in Keswick.[6] Close to the time Wordsworth and Coleridge climbed the Skiddaw mountain, 3 April 1802, Wordsworth recited the four stanzas of the ode that were completed. The poem impressed Coleridge,[7] and, while with Wordsworth, he was able to provide his response to the ode's question within an early draft of his poem, "Dejection: an Ode".[8] In early 1804, Wordsworth was able to return his attention to working on the ode. It was a busy beginning of the year with Wordsworth having to help Dorothy recover from an illness in addition to writing his poems. The exact time of composition is unknown, but it probably followed his work on The Prelude, which consumed much of February and was finished on 17 March. Many of the lines of the ode are similar to the lines of The Prelude Book V, and he used the rest of the ode to try to answer the question at the end of the fourth stanza.[9]

The poem was first printed in full for Wordsworth's 1807 collection of poems, Poems, in Two Volumes, under the title Ode.[10] It was the last poem of the second volume of the work,[11] and it had its own title page separating it from the rest of the poems, including the previous poem Peele Castle. Wordsworth added an epigraph just before publication, "paul majora canamus". The Latin phrase is from Virgil's Eclogue 4, meaning "let us sing a somewhat loftier song".[12] The poem was reprinted under its full title Ode: Intimation of Immortality from Recollections of Early Childhood for Wordsworth's collection Poems (1815). The reprinted version also contained an epigraph that, according to Henry Crabb Robinson, was added at Crabb's suggestion.[10] The epigraph was from "My Heart Leaps Up".[13] In 1820, Wordsworth issued The Miscellaneous Poems of William Wordsworth that collected the poems he wished to be preserved with an emphasis on ordering the poems, revising the text, and including prose that would provide the theory behind the text. The ode was the final poem of the fourth and final book, and it had its own title-page, suggesting that it was intended as the poem that would serve to represent the completion of his poetic abilities. The 1820 version also had some revisions,[14] including the removal of lines 140 and 141.[15]

The poem uses an irregular form of the Pindaric ode in 11 stanzas. The lengths of the lines and of the stanzas vary throughout the text, and the poem begins with an iambic meter. The irregularities increase throughout the poem and Stanza IX lacks a regular form before being replaced with a march-like meter in the final two stanzas. The poem also contains multiple enjambments and there is a use of an ABAB rhyme scheme that gives the poem a singsong quality. By the end of the poem, the rhymes start to become as irregular in a similar way to the meter, and the irregular Stanza IX closes with an iambic couplet. The purpose of the change in rhythm, rhyme, and style is to match the emotions expressed in the poem as it develops from idea to idea. The narration of the poem is in the style of an interior monologue,[16] and there are many aspects of the poem that connects it to Coleridge's style of poetry called "Conversation poems", especially the poem's reliance on a one sided discussion that expects a response that never comes.[17] There is also a more traditional original of the discussion style of the poem, as many of the prophetic aspects of the poem are related to the Old Testament of the Bible.[18] Additionally, the reflective and questioning aspects are similar to the Psalms and the works of Saint Augustine, and the ode contains what is reminiscent of Hebrew prayer.[19]

In terms of genre, the poem is an ode, which makes it a poem that is both prayer and contains a celebration of its subject. However, this celebration is mixed with questioning and this hinders the continuity of the poem.[20] The poem is also related to the elegy in that it mourns the loss of childhood vision,[21] and the title page of the 1807 edition emphasises the influence of Virgil's Eclogue 4.[22] Wordsworth's use of the elegy, in his poems including the "Lucy" poems, parts of The Excursion, and others, focus on individuals that protect themselves from a sense of loss by turning to nature or time. He also rejects any kind of fantasy that would take him away from reality while accepting both death and the loss of his own abilities to time while mourning over the loss.[23] However, the elegy is traditionally a private poem while Wordsworth's ode is more public in nature.[24] The poem is also related to the genre of apocalyptic writing in that it focuses on what is seen or the lack of sight. Such poems emphasise the optical sense and were common to many poems written by the Romantic poets, including his own poem The Ruined Cottage, Coleridge's "Dejection: An Ode" and Rime of the Ancient Mariner and Percy Bysshe Shelley's Hymn to Intellectual Beauty and The Zucca.[25]

The ode contains 11 stanzas split into three movements. The first movement is four stanzas long and discusses the narrator's inability to see the divine glory of nature, the problem of the poem. The second movement is four stanzas long and has a negative response to the problem. The third movement is three stanzas long and contains a positive response to the problem.[26] The ode begins by contrasting the narrator's view of the world as a child and as a man, with what was once a life interconnected to the divine fading away:[27]

In the second and third stanzas, the narrator continues by describing his surroundings and various aspects of nature that he is no longer able to feel. He feels as if he is separated from the rest of nature until he experiences a moment that brings about feelings of joy that are able to overcome his despair:[28]

The joy in stanza III slowly fades again in stanza IV as the narrator feels like there is "something that is gone".[28] As the stanza ends, the narrator asks two different questions to end the first movement of the poem. Though they appear to be similar, one asks where the visions are now ("Where is it now") while the other doesn't ("Whither is fled"), and they leave open the possibility that the visions could return:[29]

The second movement begins in stanza V by answering the question of stanza IV by describing a Platonic system of pre-existence. The narrator explains how humans start in an ideal world that slowly fades into a shadowy life:[28]

Before the light fades away as the child matures, the narrator emphasises the greatness of the child experiencing the feelings. By the beginning of stanza VIII, the child is described as a great individual,[30] and the stanza is written in the form of a prayer that praises the attributes of children:[31]

The end of stanza VIII brings about the end of a second movement within the poem. The glories of nature are only described as existing in the past, and the child's understanding of morality is already causing them to lose what they once had:[29]

The questions in Stanza IV are answered with words of despair in the second movement, but the third movement is filled with joy.[26] Stanza IX contains a mixture of affirmation of life and faith as it seemingly avoids discussing what is lost.[30] The stanza describes how a child is able to see what others do not see because children do not comprehend mortality, and the imagination allows an adult to intimate immortality and bond with his fellow man:[32]

The children on the shore represents the adult narrator's recollection of childhood, and the recollection allows for an intimation of returning to that mental state. In stanza XI, the imagination allows one to know that there are limits to the world, but it also allows for a return to a state of sympathy with the world lacking any questions or concerns:[33]

The poem concludes with an affirmation that, though changed by time, the narrator is able to be the same person he once was:[34]

The first version of the ode is similar to many of Wordsworth's spring 1802 poems. The ode is like To the Cuckoo in that both poems discuss aspects of nature common to the end of spring. Both poems were not crafted at times that the natural imagery could take place, so Wordsworth had to rely on his imagination to determine the scene. Wordsworth refers to "A timely utterance" in the third stanza, possibly the same event found in his The Rainbow, and the ode contains feelings of regret that the experience must end. This regret is joined with feelings of uneasiness that he no longer feels the same way he did as a boy. The ode reflects Wordsworth's darker feelings that he could no longer return to a peaceful state with nature. This gloomy feeling is also present in The Ruined Cottage and in Tintern Abbey.[35] Of the other 1802 poems, the ode is different from his Resolution and Independence, a poem that describes the qualities needed to become a great poet. The poem argued that a poet should not be excessive or irresponsible in behaviour and contains a sense of assurance that is not found within the original four stanzas. Instead, there is a search for such a feeling but the poem ends without certainty, which relates the ode to Coleridge's poem Dejection: An Ode.[36] When read together, Coleridge's and Wordsworth's poem form a dialogue with an emphasis on the poet's relationship with nature and humanity. However, Wordsworth's original four stanzas describing a loss is made darker in Coleridge and, to Coleridge, only humanity and love are able to help the poet.[37]

While with Wordsworth, Coleridge was able to read the poem and provide his response to the ode's question within an early draft of his poem, Dejection: an Ode. Coleridge's answer was to claim that the glory was the soul and it is a subjective answer to the question. Wordsworth took a different path as he sought to answer the poem, which was to declare that childhood contained the remnants of a beatific state and that being able to experience the beauty that remained later was something to be thankful for. The difference between the two could be attributed to the differences in the poets' childhood experiences; Coleridge suffered from various pain in his youth whereas Wordsworth's was far more pleasant. It is possible that Coleridge's earlier poem, The Mad Monk (1800) influenced the opening of the ode and that discussions between Dorothy and Wordsworth about Coleridge's childhood and painful life were influences on the crafting of the opening stanza of the poem.[38] However, the message in the ode, as with Tintern Abbey, describes the pain and suffering of life as able to dull the memory of early joy from nature but it is unable to completely destroy it.[39] The suffering leads Wordsworth to recognise what is soothing in nature, and he credits the pain as leading to a philosophical understanding of the world.[40]

The poem is similar to the conversation poems created by Coleridge, including Dejection: An Ode. The poems were not real conversations as there is no response to the narrator of the poem, but they are written as if there would be a response. The poems seek to have a response, though it never comes, and the possibility of such a voice though absence is a type of prosopopoeia. In general, Coleridge's poems discuss the cosmic as they long for a response, and it is this aspect, not a possible object of the conversation, that forms the power of the poem. Wordsworth took up the form in both Tintern Abbey and Ode: Intimations of Immortality, but he lacks the generous treatment of the narrator as found in Coleridge's poems. As a whole, Wordsworth's technique is impersonal and more logical, and the narrator is placed in the same position as the object of the conversation. The narrator of Wordsworth is more self-interested and any object beyond the narrator is kept without a possible voice and is turned into a second self of the poet. As such, the conversation has one of the participants lose his identity for the sake of the other and that individual represents loss and mortality.[41]

The expanded portion of the ode is related to the ideas expressed in Wordsworth's The Prelude Book V in their emphasis on childhood memories and a connection between the divine and humanity. To Wordsworth, the soul was created by the divine and was able to recognise the light in the world. As a person ages, they are no longer able to see the light, but they can still recognise the beauty in the world.[42] He elaborated on this belief in a note to the text: "Archimedes said that he could move the world if he had a point whereon to rest his machine. Who has not felt the same aspirations as regards the world of his own mind? Having to wield some of its elements when I was impelled to write this poem on the "Immortality of the Soul", I took hold of the notion of pre-existence as having sufficient foundation in humanity for authorising me to make for my purpose the best use I could of it as a Poet."[43] This "notion of pre-existence" is somewhat Platonic in nature, and it is the basis for Wordsworth believing that children are able to be the "best philosopher".[44] The idea was not intended as a type of metempsychosis, the reincarnation of the soul from person to person, and Wordsworth later explained that the poem was not meant to be regarded as a complete philosophical view: "In my Ode... I do not profess to give a literal representation of the state of the affections and of the moral being in childhood. I record my feelings at that time,--my absolute spirituality, my 'all-soulness,' if I may so speak. At that time I could not believe that I should lie down quietly in the grave, and that my body would moulder into dust."[45]

Wordsworth's explanation of the origin of the poem suggests that it was inspiration and passion that led to the ode's composition, and he later said that the poem was to deal with the loss of sensations and a desire to overcome the natural process of death. As for the specific passages in the poem that answer the question of the early version, two of the stanzas describe what it is like to be a child in a similar manner to his earlier poem, "To Hartley Coleridge, Six Years Old" dedicated to Coleridge's son. In the previous poem, the subject was Hartley's inability to understand death as an end to life or a separation. In the ode, the child is Wordsworth and, like Hartley or the girl described in "We are Seven", he too was unable to understand death and that inability is transformed into a metaphor for childish feelings. The later stanzas also deal with personal feelings but emphasise Wordsworth's appreciation for being able to experience the spiritual parts of the world and a desire to know what remains after the passion of childhood sensations are gone.[46] This emphasis of the self places mankind in the position of the object of prayer, possibly replacing a celebration of Christ's birth with a celebration of his own as the poem describes mankind coming from the eternal down to earth. Although this emphasis seems non-Christian, many of the poem's images are Judeo-Christian in origin.[47] Additionally, the Platonic theory of pre-existence is related to the Christian understanding of the Incarnation, which is a connection that Shelley drops when he reuses many of Wordsworth's ideas in The Triumph of Life.[48]

The idea of pre-existence within the poem contains only a limited theological component, and Wordsworth later believed that the concept was "far too shadowy a notion to be recommended to faith."[49] In 1989, Gene Ruoff argued that the idea was connected to Christian theology in that the Christian theorist Origen adopted the belief and relied on it in the development of Christian doctrine. What is missing in Origen's platonic system is Wordsworth's emphasis on childhood, which could be found in the beliefs of the Cambridge Platonists and their works, including Henry Vaughan's "The Retreate".[50] Even if the idea is not Christian, it still cannot be said that the poem lacks a theological component because the poem incorporates spiritual images of natural scenes found in childhood.[51] Among those natural scenes, the narrator includes a Hebrew prayer-like praise of God for the restoration of the soul to the body in the morning and the attributing of God's blessing to the various animals he sees. What concerns the narrator is that he is not being renewed like the animals and he is fearful over what he is missing. This is similar to a fear that is provided at the beginning of The Prelude and in Tintern Abbey. As for the understanding of the soul contained within the poem, Wordsworth is more than Platonic in that he holds an Augustinian concept of mercy that leads to the progress of the soul. Wordsworth differs from Augustine in that Wordsworth seeks in the poem to separate himself from the theory of solipsism, the belief that nothing exists outside of the mind. The soul, over time, exists in a world filled with the sublime before moving to the natural world, and the man moves from an egocentric world to a world with nature and then to a world with mankind. This system links nature with a renewal of the self.[52]

Ode: Intimations of Immortality is about childhood, but the poem doesn't completely focus on childhood or what was lost from childhood. Instead, the ode, like The Prelude and Tintern Abbey, places an emphasis on how an adult develops from a child and how being absorbed in nature inspires a deeper connection to humanity.[53] The ode focuses not on Dorothy or on Wordsworth's love, Mary Hutchinson, but on himself and is part of what is called his "egotistical sublime".[54] Of his childhood, Wordsworth told Catherine Clarkson in an 1815 letter that the poem "rests entirely upon two recollections of childhood, one that of a splendour in the objects of sense which is passed away, and the other an indisposition to bend to the law of death as applying to our particular case.... A Reader who has not a vivid recollection of these feelings having existed in his mind in childhood cannot understand the poem."[55] Childhood, therefore, becomes a means to exploring memory, and the imagination, as Wordsworth claims in the letter, is connected to man's understanding of immortality. In a letter to Isabella Fenwick, he explained his particular feelings about immortality that he held when young:[56] "I was often unable to think of external things as having external existence, and I communed with all that I saw as something not apart from, but inherent in, my own immaterial nature."[57] These feelings were influenced by Wordsworth's own experience of loss, including the death of his parents, and may have isolated him from society if the feelings did not ease as he matured.[58]

Like the two other poems, The Prelude and Tintern Abbey, the ode discusses Wordsworth's understanding of his own psychological development, but it is not a scientific study of the subject. He believed that it is difficult to understand the soul and emphasises the psychological basis of his visionary abilities, an idea found in the ode but in the form of a lamentation for the loss of vision. To Wordsworth, vision is found in childhood but is lost later, and there are three types of people that lose their vision. The first are men corrupted through either an apathetic view of the visions or through meanness of mind. The second are the "common" people who lose their vision as a natural part of ageing. The last, the gifted, lose parts of their vision, and all three retain at least a limited ability to experience visions. Wordsworth sets up multiple stages, infancy, childhood, adolescence, and maturity as times of development but there is no real boundary between each stage. To Wordsworth, infancy is when the "poetic spirit", the ability to experience visions, is first developed and is based on the infant learning about the world and bonding to nature. As the child goes through adolescence, he continues to bond with nature and this is slowly replaced by a love for humanity, a concept known as "One Life". This leads to the individual despairing and only being able to resist despair through imagination.[59] When describing the stages of human life, one of the images Wordsworth relies on to describe the negative aspects of development is a theatre stage, the Latin idea of theatrum mundi. The idea allows the narrator to claim that people are weighed down by the roles they play over time. The narrator is also able to claim through the metaphor that people are disconnected from reality and see life as if in a dream.[60]

Wordsworth returns to the ideas found within the complete ode many times in his later works. There is also a strong connection between the ode and Wordsworth's Ode to Duty, completed at the same time in 1804. The poems describe Wordsworth's assessment of his poetry and contains reflections on conversations held between Wordsworth and Coleridge on poetry and philosophy. The basis of the Ode to Duty states that love and happiness are important to life, but there is something else necessary to connect an individual to nature, affirming the narrator's loyalty to a benevolent divine presence in the world. However, Wordsworth was never satisfied with the result of Ode to Duty as he was with Ode: Intimations on Immortality.[61] In terms of use of light as a central image, the ode is related to Peele Castle, but the light in the latter poem is seen as an illusion and stands in opposition to the ode's ideas.[62] In an 1809 essay as part of his Essays upon Epitaphs for Coleridge's journal, The Friend, Wordsworth argued that people have intimations that there is an immortal aspect of their life and that without such feelings that joy could not be felt in the world. The argument and the ideas are similar to many of the statements in the ode along with those in The Prelude, Tintern Abbey, and "We Are Seven". He would also return directly to the ode in his 1817 poem Composed upon an Evening of Extraordinary Splendor and Beauty where he evaluates his own evolving life and poetic works while discussing the loss of an early vision of the world's joys. In the Ode: Intimations on Immortality, Wordsworth concluded that he gives thanks that was able to gain even though he lost his vision of the joy in the world, but in the later work he tones down his emphasis on the gain and provides only a muted thanks for what remains of his ability to see the glory in the world.[63]

Wordsworth's ode is a poem that describes how suffering allows for growth and an understanding of nature,[40] and this belief influenced the poetry of other Romantic poets. Wordsworth followed a Virgilian idea called lachrimae rerum, which means that "life is growth" but it implies that there is also loss within life. To Wordsworth, the loss brought about enough to make up for what was taken. Shelley, in his Prometheus Unbound, describes a reality that would be the best that could be developed but always has the suffering, death, and change. John Keats developed an idea called "the Burden of the Mystery" that emphasizes the importance of suffering in the development of man and necessary for maturation.[64] However, Coleridge's Dejection: An Ode describes the loss of his own poetic ability as he aged and mourned what time took. In Coleridge's theory, his poetic abilities were the basis for happiness and without them there would only be misery.[65] In addition to views on suffering, Shelley relies on Wordsworth's idea of pre-existence in The Triumph of Life,[48] and Keats relies on Wordsworth's interrogative technique in many of his poems, but he discards the egocentric aspects of the questions.[66]

The ode praises children for being the "best Philosopher" ("lover of truth") because they live in truth and have prophetic abilities.[31] This claim bothers Coleridge and he writes, in Biographia Literaria, that Wordsworth was trying to be a prophet in an area that he could have no claim to prophecy.[67] In his analysis of the poem, Coleridge breaks down many aspects of Wordsworth's claims and asks, "In what sense can the magnificent attributes, above quoted, be appropriated to a child, which would not make them equally suitable to a be, or a dog, or a field of corn: or even to a ship, or to the wind and waves that propel it? The omnipresent Spirit works equally in them, as in the child; and the child is equally unconscious of it as they."[68] The knowledge of nature that Wordsworth thinks is wonderful in children, Coleridge feels is absurd in Wordsworth since a poet couldn't know how to make sense of a child's ability to sense the divine any more than the child with a limited understanding could know of the world.[69] I. A. Richards, in his work Coleridge on Imagination (1934), responds to Coleridge's claims by asking, "Why should Wordsworth deny that, in a much less degree, these attributes are equally suitable to a bee, or a dog, or a field of corn?"[70]

Later, Cleanth Brooks reanalyzes the argument to point out that Wordsworth would include the animals among the children. He also explains that the child is the "best philosopher" because of his understanding of the "eternal deep", which comes from enjoying the world through play: "They are playing with their little spades and sand-buckets along the beach on which the waves break."[71] In 1992, Susan Eilenberg returned to the dispute and defended Coleridge's analysis by explaining that "It exhibits the workings of the ambivalence Coleridge feels toward the character of Wordsworth's poetry; only now, confronting greater poetry, his uneasiness is greater... If Wordsworth's weakness is incongruity, his strength is propriety. That Coleridge should tell us this at such length tells as much about Coleridge as about Wordsworth: reading the second volume of the Biographia, we learn not only Wordsworth's strong and weak points but also the qualities that most interest Coleridge."[72]

The Ode: Intimations of Immortality is the most celebrated poem published in Wordsworth's Poems in Two Volumes collection. While modern critics believe that the poems published in Wordsworth's 1807 collection represented a productive and good period of his career, contemporary reviewers were split on the matter and many negative reviews cast doubts on his circle of poets known as the Lake Poets. Negative reviews were found in the Critical Review, Le Beau Monde and Literary Annual Register.[73]George Gordon Byron, a fellow Romantic poet but not an associate of Wordsworth's, responded to Poems in Two Volumes, in a 3 July 1807 Monthly Literary Recreations review, with a claim that the collection lacked the quality found in Lyrical Ballads.[74] When referring to Ode: Intimations of Immortality, he dismissed the poem as Wordsworth's "innocent odes" without providing any in-depth response, stating only: "On the whole, however, with the exception of the above, and other innocent odes of the same cast, we think these volumes display a genius worthy of higher pursuits, and regret that Mr. W. confines his muse to such trifling subjects... Many, with inferior abilities, have acquired a loftier seat on Parnassus, merely by attempting strains in which Mr. W. is more qualified to excel."[75] The poem was received negatively but for a different reason from Wordsworth's and Coleridge's friend Robert Southey, also a Romantic poet. Southey, in an 8 December 1807 letter to Walter Scott, wrote, "There are certainly some pieces there which are good for nothing... and very many which it was highly injudicious to publish.... The Ode upon Pre-existence is a dark subject darkly handled. Coleridge is the only man who could make such a subject luminous."[76]

Francis Jeffrey, a Whig lawyer and editor of the Edinburgh Review, originally favoured Wordsworth's poetry following the publication of Lyrical Ballads in 1798 but turned against the poet from 1802 onward. In response to Wordsworth's 1807 collection of poetry, Jeffrey contributed an anonymous review to the October 1807 Edinburgh Review that condemned Wordsworth's poetry again.[77] In particular, he declared the ode "beyond all doubt, the most illegible and unintelligible part of the publication. We can pretend to give no analysis or explanation of it;-- our readers must make what they can of the following extracts."[78] After quoting the passage, he argues that he has provided enough information for people to judge if Wordsworth's new school of poetry should be replace the previous system of poetry: "If we were to stop here, we do not think that Mr Wordsworth, or his admirers, would have any reason to complain; for what we have now quoted is undeniably the most peculiar and characteristic part of his publication, and must be defended and applauded if the merit or originality of his system is to be seriously maintained.[78] In putting forth his own opinion, Jeffrey explains, "In our own opinion, however, the demerit of that system cannot be fairly appretiated, until it be shown, that the author of the bad verses which we have already extracted, can write good verses when he pleases".[78] Jeffrey later wrote a semi-positive review of the ode, for the 12 April 1808 Edinburgh Review, that praised Wordsworth when he was least Romantic in his poetry. He believed that Wordsworth's greatest weakness was portraying the low aspects of life in a lofty tone.[74]

Another semi-negative response to the poem followed on 4 January 1808 in the Eclectic Review. The writer, James Montgomery, attacked the 1807 collection of poems for depicting low subjects. When it came to the ode, Montgomery attacked the poem for depicting pre-existence.[74] After quoting the poem with extracts from the whole collection, he claimed, "We need insist no more on the necessity of using, in poetry, a language different from and superior to 'the real language of men,' since Mr. Wordsworth himself is so frequently compelled to employ it, for the expression of thoughts which without it would be incommunicable. These volumes are distinguished by the same blemishes and beauties as were found in their predecessors, but in an inverse proportion: the defects of the poet, in this performance, being as much greater than his merits, as they were less in his former publication."[79] In his conclusion, Montgomery returned to the ode and claimed, that "the reader is turned loose into a wilderness of sublimity, tenderness, bombast, and absurdity, to find out the subject as well as he can... After our preliminary remarks on Mr. Wordsworth's theory of poetical language, and the quotations which we have given from these and his earlier compositions, it will be unnecessary to offer any further estimate or character of his genius. We shall only add one remark.... Of the pieces now published he has said nothing: most of them seem to have been written for no purpose at all, and certainly to no good one."[80] In January 1815, Montgomery returned to Wordsworth's poetry in another review and argues, "Mr. Wordsworth often speaks in ecstatic strains of the pleasure of infancy. If we rightly understand him, he conjectures that the soul comes immediately from a world of pure felicity, when it is born into this troublous scene of care and vicissitude... This brilliant allegory, (for such we must regard it,) is employed to illustrate the mournful truth, that looking back from middle age to the earliest period of remembrance we find, 'That there hath pass'd away a glory from the earth,'... Such is Life".[81]

John Taylor Coleridge, nephew to Samuel Taylor Coleridge, submitted an anonymous review for the April 1814 Quarterly Review. Though it was a review of his uncle's Remorse, he connects the intention and imagery found within Coleridge's poem to that in Ode: Intimation of Immortality and John Wilson's "To a Sleeping Child" when saying, "To an extension or rather a modification of this last mentioned principle [obedience to some internal feeling] may perhaps be attributed the beautiful tenet so strongly inculcated by them of the celestial purity of infancy. 'Heaven lies about us in our infancy,' says Mr. Wordsworth, in a passage which strikingly exemplifies the power of imaginative poetry".[82] John Taylor Coleridge returned to Wordsworth's poetry and the ode in a May 1815 review for the British Critic. In the review, he partially condemns Wordsworth's emphasis in the ode on children being connected to the divine: "His occasional lapses into childish and trivial allusion may be accounted for, from the same tendency. He is obscure, when he leaves out links in the chain of association, which the reader cannot easily supply... In his descriptions of children this is particularly the case, because of his firm belief in a doctrine, more poetical perhaps, than either philosophical or christian, that 'Heaven lies about us in our infancy.'"[83]

John Taylor Coleridge continues by explaining the negative aspects of such a concept: "Though the tenderness and beauty resulting from this opinion be to us a rich overpayment for the occasional strainings and refinements of sentiment to which it has given birth, it has yet often served to make the author ridiculous in common eyes, in that it has led him to state his own fairy dreams as the true interpretation and import of the looks and movements of children, as being even really in their minds."[83] In a February 1821 review for the British Critic, John Taylor Coleridge attacked the poem again for a heretical view found in the notion of pre-existence and how it reappeared in Wordsworth's poem "On an Extraordinary Evening of Splendour and Beauty".[84] However, he does claim that the passage of the ode containing the idea is "a passage of exquisite poetry" and that "A more poetical theory of human nature cannot well be devised, and if the subject were one, upon which error was safe, we should forbear to examine it closely, and yield to the delight we have often received from it in the ode from which the last extract [Ode: Intimations of Immortality] is made."[85] He was to continue: "If, therefore, we had met the doctrine in any poet but Mr. Wordsworth, we should have said nothing; but we believe him to be one not willing to promulgate error, even in poetry, indeed it is manifest that he makes his poetry subservient to his philosophy; and this particular notion is so mixed up by him with others, in which it is impossible to suppose him otherwise than serious; that we are constrained to take it for his real and sober belief."[85]

In the same year came responses to the ode by two Romantic writers. Leigh Hunt, a second-generation Romantic poet, added notes to his poem Feast of the Poets that respond to the ideas suggested in Wordsworth's poetry. These ideas include Wordsworth's promotion of a simple mental state without cravings for knowledge, and it is such an ideas that Hunt wanted to mock in his poem. However, Hunt did not disagree completely with Wordsworth's sentiments. After quoting the final lines of the Ode: Intimations of Immortality, those that "Wordsworth has beautifully told us, that to him '--the meanest flow'r that blows can give/ Thoughts that do often lie too deep for tears", Hunt claims, "I have no doubt of it; and far be it from me to cast stones into the well in which they lie,-- to disturb those reposing waters,-- that freshness at the bottom of warm hearts,-- those thoughts, which if they are too deep for tears, are also, in their best mood, too tranquil even for smiles. Far be it also from me to hinder the communication of such thoughts to mankind, when they are not sunk beyond their proper depth, so as to make one dizzy in looking down to them."[86] Following Hunt, William Hazlitt, a critic and Romantic writer, wrote a series of essays called "Character of Mr. Wordsworth's New Poems" in three parts, starting in the 21 August 1814 Examiner. Although Hazlitt treated Wordsworth's poetry fairly, he was critical of Wordsworth himself and he removed any positive statements about Wordsworth's person from a reprint of the essays.[87] The 2 October 1814 essay examined poetry as either of imagination or of sentiment, and quotes the final lines of the poem as an example of "The extreme simplicity which some persons have objected to in Mr. Wordsworth's poetry is to be found only in the subject and style: the sentiments are subtle and profound. In the latter respect, his poetry is as much above the common standard or capacity, as in the other it is below it... We go along with him, while he is the subject of his own narrative, but we take leave of him when he makes pedlars and ploughmen his heroes and the interpreters of his sentiments."[88]

In 1817 came two more responses by Romantic poets to the ode. Coleridge was impressed by the ode's themes, rhythm, and structure since he first heard the beginning stanzas in 1802.[89] In an analysis of Wordsworth's poetry for his work Biographia Literaria (1817), Coleridge described what he considered as both the positives and the defects of the ode. In his argument, he both defended his technique and explained: "Though the instances of this defect in Mr. Wordsworth's poems are so few, that for themselves it would have been scarce just to attract the reader's attention toward them; yet I have dwelt on it, and perhaps the more for this very reason. For being so very few, they cannot sensibly detract from the reputation of an author, who is even characterized by the number of profound truths in his writings, which will stand the severest analysis; and yet few as they are, they are exactly those passages which his blind admirers would be most likely, and best able, to imitate."[90] Of the positives that Coleridge identified within the poem, he placed emphasis on Wordsworth's choice of grammar and language that established a verbal purity in which the words chosen could not be substituted without destroying the beauty of the poem. Another aspect Coleridge favoured was the poem's originality of thought and how it contained Wordsworth's understanding of nature and his own experience. Coleridge also praised the lack of a rigorous structure within the poem and claimed that Wordsworth was able to truly capture the imagination. However, part of Coleridge's analysis of the poem and of the poet tend to describe his idealised version of positives and negative than an actual concrete object.[91] In the same year, it was claimed by Benjamin Bailey, in a 7 May 1849 letter to R. M. Milnes, that John Keats, one of the second-generation Romantic poets, discussed the poem with him. In his recollection, Bailey said, "The following passage from Wordsworth's ode on Immortality [lines 140148] was deeply felt by Keats, who however at this time seemed to me to value this great Poet rather in particular passages than in the full length portrait, as it were, of the great imaginative & philosophic Christian Poet, which he really is, & which Keats obviously, not long afterwards, felt him to be."[92]

Following Coleridge's response was an anonymous review in the May 1820 Blackwood's Edinburgh Magazine, possible by either John Lockhart and John Wilson together or just Lockhart on his own. Of Wordsworth's abilities as a poet in general, the review claimed: "Mr Wordsworth ... is entitled to be classed with the very highest names among his predecessors, as a pure and reverent worshipper of the true majest of the English Muse" and that "Of the genius of Mr Wordsworth, in short, it is now in the hands of every man to judge freely and fully, and for himself. Our own opinion, ever since this Journal commenced, has been clearly and entirely before them; and if there be any one person, on whose mind what we have quoted now, is not enough to make an impression similar to that which our own judgment had long before received we have nothing more to say to that person in regard to the subject of poetry."[93] In discussing the ode in particular, the review characterised the poem as "one of the grandest of his early pieces".[94] In December 1820 came an article in the New Monthly Magazine titled "On the Genius and Writings of Wordsworth" written by Thomas Noon Talfourd. When discussing the poem, Talfourd declared that the ode "is, to our feelings, the noblest piece of lyric poetry in the world. It was the first poem of its author which we read, and never shall we forget the sensations which it excited within us. We had heard the cold sneers attached to his name... and here in the works of this derided poet we found a new vein of imaginative sentiment open to us sacred recollections brought back to our hearts with all the freshness of novelty, and all the venerableness of far-off time".[95] When analysing the relationship between infants and the divine within the poem, the article continued: "What a gift did we then inherit! To have the best and most imperishable of intellectual treasures the mighty world of reminiscences of the days of infancy set before us in a new and holier light".[96]

William Blake, a Romantic poet and artist, thought that Wordsworth was at the same level as the poets Dante, Shakespeare, and Milton. In a diary entry for 27 December 1825, H. C. Robinson recounted a conversation between himself and William Blake shortly before Blake's death: "I read to him Wordsworth's incomparable ode, which he heartily enjoyed. But he repeated, 'I fear Wordsworth loves nature, and nature is the work of the Devil. The Devil is in us as 'far as we are nature.'... The parts of Wordsworth's ode which Blake most enjoyed were the most obscureat all events, those which I least like and comprehend."[97] Following Blake, Chauncy Hare Townshend produced "An Essay on the Theory and the Writings of Wordsworth"for Blackwood's Edinburgh Magazine in 1829. In the third part, he critiqued Wordsworth's use of pre-existence within the poem and asked "unless our author means to say that, having existed from all eternity, we are of an eternal and indestructible essence; or, in other words, that being incarnate portion of the Deity... we are as Immortal as himself. But if the poet intends to affirm this, do you not perceive that he frustrates his own aim?"[98] He continued by explaining why he felt that Wordsworth's concept fell short of any useful purpose: "For if we are of God's indivisible essence, and receive our separate consciousness from the wall of flesh which, at our birth, was raised between us and the Found of Being, we must, on the dissolution of the body... be again merged in the simple and uncompounded Godhead, lose our individual consciousness... in another sense, become as though we had never been."[98] He concluded his analysis with a critique of the poem as a whole: "I should say that Wordsworth does not display in it any great clearness of thought, or felicity of language... the ode in question is not so much abstruse in idea as crabbed in expression. There appears to be a laborious toiling after originality, ending in a dismal want of harmony."[98]

The ode, like others of Wordsworth's poetry, was favoured by Victorians for its biographical aspects and the way Wordsworth approached feelings of despondency. The American Romantic poet Ralph Waldo Emerson, in his 1856 work English Traits, claimed that the poem "There are torpid places in his mind, there is something hard and sterile in his poetry, want of grace and variety, want of due catholicity and cosmopolitan scope: he had conformities to English politics and tradition; he had egotistic puerilities in the choice and treatment of his subjects; but let us say of him, that, alone in his time he treated the human mind well, and with an absolute trust. His adherence to his poetic creed rested on real inspirations."[99] The editor of Harper's New Monthly Magazine, George William Curtis, praised the ode in his December 1859 column "Editor's Easy Chair" and claimed that "it was Wordsworth who has written one of the greatest English poets... For sustained splendor of imagination, deep, solemn, and progressive thought, and exquisite variety of music, that poem is unsurpassed. Since Milton's 'Ode upon the Nativity' there is nothing so fine, not forgetting Dryden, Pope, Collins, and the rest, who have written odes."[100]

The philosopher John Stuart Mill liked Wordsworth's ode and found it influential to the formation of his own thoughts. In his Autobiography (1873), he credited Wordsworth's poetry as being able to relieve his mind and overcome a sense of apathy towards life. Of the poems, he particularly emphasised both Wordsworth's 1815 collection of poetry and the Ode: Intimations of Immortality as providing the most help to him, and he specifically said of the ode: "I found that he too had had similar experience to mine; that he also had felt that the first freshness of youthful enjoyment of life was not lasting; but that he had sought for compensation, and found it, in the way in which he was now teaching me to find it. The result was that I gradually, but completely, emerged from my habitual depression, and was never again subject to it."[101] David Mason followed Mill in an 1875 essay on literature, including Wordsworth's poetry. After quoting from the ode, Mason claimed of the poem: "These, and hundreds of other passages that might be quoted, show that Wordsworth possessed, in a very high degree indeed, the true primary quality of the poetimagination; a surcharge of personality or vital spirit, perpetually overflowing among the objects of the otherwise conditioned universe, and refashioning them according to its pleasure."[102]

After Mill, critics focused on the ode's status among Wordsworth's other poems. In July 1877, Edward Dowden, in an article for the Contemporary Review, discussed the Transcendental Movement and the nature of the Romantic poets. when referring to Wordsworth and the ode, he claimed: "Wordsworth in his later years lost, as he expresses it, courage, the spring-like hope and confidence which enables a man to advance joyously towards new discovery of truth. But the poet of 'Tintern Abbey' and the 'Ode on Intimations of Immortality' and the 'Prelude' is Wordsworth in his period of highest energy and imaginative light".[103] Matthew Arnold, in his preface to an 1879 edition of Wordsworth's poetry, explains that he was a great lover of the poems. However, he explains why he believed that the ode was not one of the best: "I have a warm admiration for Laodameia and for the great Ode; but if I am to tell the very truth, I find Laodameia not wholly free from something artificial, and the great Ode not wholly free from something declamatory."[104] His concern was over what he saw as the ideas expressed on childhood and maturity: "Even the 'intimations' of the famous Ode, those corner-stones of the supposed philosophic system of Wordsworth... has itself not the character of poetic truth of the best kind; it has no real solidity" "to say that universally this instinct is mighty in childhood, and tends to die away afterwards, is to say what is extremely doubtful... In general, we may say of these high instincts of early childhood... what Thucydides says of the early achievements of the Greek race:--'It is impossible to speak with certainty of what is so remove; but from all that we can really investigate, I should say that they were no very great things.'"[105]

The Victorian critic John Ruskin, towards the end of the 19th century, provided short analyses of various writers in his "Nature and Literature" essays collected in "Art and Life: a Ruskin Anthology". In speaking of Wordsworth, Ruskin claimed, "Wordsworth is simply a Westmoreland peasant, with considerably less shrewdness than most border Englishmen or Scotsmen inherit; and no sense of humor; but gifted... with vivid sense of natural beauty, and a pretty turn for reflection, not always acute, but, as far as they reach, medicinal to the fever of the restless and corrupted life around him."[106] After mocking the self-reflective nature of Wordsworth's poetry, he then declared that the poetry was "Tuneful nevertheless at heart, and of the heavenly choir, I gladly and frankly acknowledge him; and our English literature enriched with a new and singular virtue in the aerial purity and healthful rightness of his quiet song;but aerial onlynot ethereal; and lowly in its privacy of light". The ode, to Ruskin, becomes a means to deride Wordsworth's intellect and faith when he claims that Wordsworth was "content with intimations of immortality such as may be in skipping of lambs, and laughter of children-incurious to see in the hands the print of the nails."[106] Ruskin's claims were responded to by an article by Richard Hutton in the 7 August 1880 Spectator.[107] The article, "Mr. Ruskin on Wordsworth", stated, "We should hardly have expected Mr. Ruskina great master of irony though he beto lay his finger so unerringly as he does on the weak point of Wordsworth's sublime ode on the 'Intimations of Immortality,' when he speaks of himquite falsely, by the wayas 'content with intimations of immortality'".[108] The article continued with praise of Wordsworth and condemns Ruskin further: "But then, though he shows how little he understands the ode, in speaking of Wordsworth as content with such intimations, he undoubtedly does touch the weak chord in what, but for that weak chord, would be one of the greatest of all monuments of human genius... But any one to whom Wordsworth's great ode is the very core of that body of poetry which makes up the best part of his imaginative life, will be as much astonished to find Mr. Ruskin speaking of it so blindly and unmeaningly as he does".[108]

The ode was viewed positively by the end of the century. George Saintsbury, in his A Short History of English Literature (1898), declared the importance and greatness of the ode: "Perhaps twice only, in Tintern Abbey and in the Ode on the Intimations of Immortality, is the full, the perfect Wordsworth, with his half-pantheistic worship of nature, informed and chastened by an intense sense of human conduct, of reverence and almost of humbleness, displayed in the utmost poetic felicity. And these two are accordingly among the great poems of the world. No unfavorable criticism on either and there has been some, new and old, from persons in whom it is surprising, as well as from persons in whom it is natural has hurt them, though it may have hurt the critics. They are, if not in every smallest detail, yet as wholes, invulnerable and imperishable. They could not be better done."[109]

At the beginning of the 20th century, response to the ode by critics was mostly positive. Andrew Bradley declared in 1909 that "The Immortality Ode, like King Lear, is its author's greatest product, but not his best piece of work."[110] When speaking of Grasmere and Wordsworth, Elias Sneath wrote in 1912: "It witnessed the composition of a large number of poems, many of which may be regarded among the finest products of his imagination. Most of them have already been considered. However, one remains which, in the judgment of some critics, more than any other poem of the numerous creations of his genius, entitles him to a seat among the Immortals. This is the celebrated [ode]... It is, in some respects, one of his most important works, whether viewed from the stand point of mere art, or from that of poetic insight."[111] George Harper, following Sneath in 1916, described the poem in positive terms and said, "Its radiance comes and goes through a shimmering veil. Yet, when we look close, we find nothing unreal or unfinished. This beauty, though supernal, is not evanescent. It bides our return, and whoever comes to seek it as a little child will find it. The imagery, though changing at every turn, is fresh and simple. The language, though connected with thoughts so serious that they impart to it a classic dignity, is natural and for the most part plain.... Nevertheless, a peculiar glamour surrounds the poem. It is the supreme example of what I may venture to term the romance of philosophic thought."[112]

The 1930s contained criticism that praised the poem, but most critics found fault with particular aspects of the poem. F. R. Leavis, in his Revaluation (1936), argued that "Criticism of Stanza VIII ... has been permissible, even correct, since Coleridge's time. But the empty grandiosity apparent there is merely the local manifestation of a general strain, a general factitiousness. The Ode... belongs to the transition at its critical phase, and contains decided elements of the living."[113] He continued, "But these do not lessen the dissatisfaction that one feels with the movementthe movement that makes the piece an ode in the Grand Style; for, as one reads, it is in terms of the movement that the strain, the falsity, first asserts itself. The manipulations by which the change of mood are indicated have, by the end of the third stanza, produced an effect that, in protest, one described as rhythmic vulgarity..., and the strain revealed in technique has an obvious significance".[113] In 1939, Basil Willey argued that the poem was "greatly superior, as poetry, to its psychological counterpart in The Prelude" but also said that "the semi-Platonic machinery of pre-existence... seems intrusive, and foreign to Wordsworth" before concluding that the poem was the "final and definitive expression to the most poignant experience of his poetic life".[114]

Cleanth Brooks used the Ode: Intimation of Immortality as one of his key works to analyse in his 1947 work The Well Wrought Urn. His analysis broke down the ode as a poem disconnected from its biographical implications and focused on the paradoxes and ironies contained within the language. In introducing his analysis, he claimed that it "may be surmised from what has already been remarked, the 'Ode' for all its fine passages, is not entirely successful as a poem. Yet, we shall be able to make our best defense of it in proportion as we recognize and value its use of ambiguous symbol and paradoxical statement. Indeed, it might be maintained that, failing to do this, we shall miss much of its power as poetry and even some of its accuracy of statement."[115] After breaking down the use of paradox and irony in language, he analyses the statements about the childhood perception of glory in Stanza VI and argued, "This stanza, though not one of the celebrated stanzas of the poem, is one of the most finely ironical. Its structural significance too is of first importance, and has perhaps in the past been given too little weight."[116] After analysing more of the poem, Brooks points out that the lines in Stanza IX contains lines that "are great poetry. They are great poetry because ... the children are not terrified... The children exemplify the attitude toward eternity which the other philosopher, the mature philosopher, wins to with difficulty, if he wins to it at all."[117] In his conclusion about the poem, he argues, "The greatness of the 'Ode' lies in the fact that Wordsworth is about the poet's business here, and is not trying to inculcate anything. Instead, he is trying to dramatize the changing interrelations which determine the major imagery."[118] Following Brooks in 1949, C. M. Bowra stated, "There is no need to dispute the honour in which by common consent it [the ode] is held" but he adds "There are passages in the 'Immortal Ode' which have less than his usual command of rhythm and ability to make a line stand by itself... But these are unimportant. The whole has a capacious sweep, and the form suits the majestic subject... There are moments when we suspect Wordsworth of trying to say more than he means.[119] Similarly, George Mallarby also revealed some flaws in the poem in his 1950 analysis: "In spite of the doubtful philosophical truth of the doctrine of pre-existence borrowed from Platon, in spite of the curiously placed emphasis and an exuberance of feeling somewhat artificially introduced, in spite of the frustrating and unsatisfying conclusion, this poem will remain, so long as the English language remains, one of its chief and unquestionable glories. It lends itself, more than most English odes, to recitation in the grand manner."[120]

By the 1960s and 1970s, the reception of the poem was mixed but remained overall positive. Mary Moorman analysed the poem in 1965 with an emphasis on its biographical origins and Wordsworth's philosophy on the relationship between mankind and nature. When describing the beauty of the poem, she stated, "Wordsworth once spoke of the Ode as 'this famous, ambitious and occasionally magnificent poem'. Yet it is not so much its magnificence that impresses, as the sense of resplendent yet peaceful light in which it is bathedwhether it is the 'celestial light' and 'glory' of the first stanza, or the 'innocent Brightness of a new-born Day' of the last."[121] In 1967, Yvor Winters criticised the poem and claimed that "Wordsworth gives us bad oratory about his own clumsy emotions and a landscape that he has never fully realized."[122] Geoffrey Durrant, in his 1970 analysis of the critical reception of the ode, claimed, "it may be remarked that both the admirers of the Ode, and those who think less well of it, tend to agree that it is unrepresentative, and that its enthusiastic, Dionysian, and mystical vein sets it apart, either on a lonely summit or in a special limbo, from the rest of Wordsworth's work. And the praise that it has received is at times curiously equivocal."[123] In 1975, Richard Brantley, labelling the poem as the "great Ode", claimed that "Wordsworth's task of tracing spiritual maturity, his account of a grace quite as amazing and perhaps even as Christian as the experience recorded in the spiritual autobiography of his day, is therefore essentially completed".[1] He continued by using the ode as evidence that the "poetic record of his remaining life gives little evidence of temptations or errors as unsettling as the ones he faced and made in France."[1] Summarizing the way critics have approached the poem, John Beer claimed in 1978 that the poem "is commonly regarded as the greatest of his shorter works".[3] Additionally, Beer argued that the ode was the basis for the concepts found in Wordsworth's later poetry.[124]

Criticism of the ode during the 1980s ranged in emphasis on which aspects of the poem were most important, but critics were mostly positive regardless of their approach. In 1980, Hunter Davies analysed the period of time when Wordsworth worked on the ode and included it as one of the "scores of poems of unarguable genius",[125] and later declared the poem Wordsworth's "greatest ode".[2] Stephen Gill, in a study of the style of the 1802 poems, argued in 1989 that the poems were new and broad in range with the ode containing "impassioned sublimity".[126] He later compared the ode with Wordsworth's "Ode to Duty" to declare that "The Ode: Intimations, by contrast, rich in phrases that have entered the language and provided titles for other people's books, is Wordsworth's greatest achievement in rhythm and cadence. Together with Tintern Abbey it has always commanded attention as Wordsworth's strongest meditative poem and Wordsworth indicated his assessment of it by ensuring through the layout and printing of his volumes that the Ode stood apart."[127] In 1986, Marjorie Levinson searched for a political basis in many of Wordsworth's poems and argued that the ode, along with "Michael", Peele Castle, and Tintern Abbey, are "incontestably among the poet's greatest works".[128] Susan Wolfson, in the same year, claimed that "the force of the last lines arises from the way the language in which the poet expresses a resolution of grief at the same time renders a metaphor that implies that grief has not been resolved so much as repressed and buried. And this ambiguity involves another, for Wordsworth makes it impossible to decide whether the tension between resolution and repression... is his indirect confession of a failure to achieve transcendence or a knowing evasion of an imperative to do so."[129] After performing a Freudian-based analysis of the ode, William Galperin, in 1989, argues that "Criticism, in short, cannot accept responsibility for The Excursion's failings any more than it is likely to attribute the success of the 'Intimations Ode' to the satisfaction it offers in seeing a sense of entitlement, or self-worth, defended rather than challenged."[130]

1990s critics emphasised individual images within the poem along with Wordsworth's message being the source of the poem's power. In 1991, John Hayden updated Russell Noyes's 1971 biography of Wordsworth and began his analysis of the ode by claiming: "Wordsworth's great 'Ode on Immortality' is not easy to follow nor wholly clear. A basic difficulty of interpretation centers upon what the poet means by 'immortality.'"[131] However, he goes on to declare, "the majority of competent judges acclaim the 'Ode on Immortality' as Wordsworth's most splendid poem. In no other poem are poetic conditions so perfectly fulfilled. There is the right subject, the right imagery to express it, and the right meter and language for both."[132] Thomas McFarland, when emphasising the use of a river as a standard theme in Wordsworth's poems, stated in 1992: "Not only do Wordsworth's greatest statements--'Tintern Abbey', 'The Immortality Ode', 'The Ruined Cottage', 'Michael', the first two books of The Prelude--all overlie a streaming infrashape, but Wordsworth, like the other Romantics, seemed virtually hypnotized by the idea of running water."[133] After analysing the Wordsworth's incorporation of childhood memories into the ode, G. Kim Blank, in 1995, argued, "It is the recognition and finally the acceptance of his difficult feelings that stand behind and in the greatness and power of the Ode, both as a personal utterance and a universal statement. It is no accident that Wordsworth is here most eloquent. Becoming a whole person is the most powerful statement any of us can ever made. Wordsworth in the Ode here makes it for us."[134] In 1997, John Mahoney praised the various aspects of the poem while breaking down its rhythm and style. In particular, he emphasised the poem's full title as "of great importance for all who study the poem carefully" and claimed, "The final stanza is a powerful and peculiarly Wordsworthian valediction."[135]

In the 21st century, the poem was viewed as Wordsworth's best work. Adam Sisman, in 2007, claimed the poem as "one of [Wordsworth's] greatest works".[136] Following in 2008, Paul Fry argued, "Most readers agree that the Platonism of the Intimations Ode is foreign to Wordsworth, and express uneasiness that his most famous poem, the one he always accorded its special place in arranging his successive editions, is also so idiosyncratic."[137] He continued, "As Simplon and Snowdon also suggest, it was a matter of achieving heights (not the depth of 'Tintern Abbey'), and for that reason the metaphor comes easily when one speaks of the Intimations Ode as a high point in Wordsworth's career, to be highlighted in any new addition as a pinnacle of accomplishment, a poem of the transcendental imagination par excellence."[138]

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6 Reasons to Supplement With Resveratrol | Men’s Fitness

Its a fact, not all foods and supplements receive the same share of the spotlight, attention, or scrutiny. In spite of the ample scientific research behind it, one of the most overlooked is resveratrol. It may surprise you to learn that resveratrol, most commonly associated with wine, has many benefits that may not only help you in your next trip to the gym, but could also you enhance your opportunity to age more gracefully. Weve compiled a list of the top six benefits of resveratrol, and some helpful strategies to maximize your efforts.

Do you get turned off with the mere thought of endurance training? What if you could enhance your results? According to a 2012 Canadian study, resveratrol supplementation could provide similar skeletal muscle benefits as endurance training. The study, conducted over a 12-week period on rats, found that resveratrol supplementation also resulted in an increase of endurance, oxidative metabolism, and enhanced cardiac function. Better yet, the combination of endurance training with resveratrol supplementation resulted in a performance increase of 21%. Be smart: Continue endurance training and consider resveratrol supplementation to augment results.

According to the Center for Disease Control and Prevention, in 2011, heart disease ranked as the United States leading cause of death. Consider your family history and plan ahead. A Canadian study found that by drinking one to two 5-ounce glasses of wine per day, study participants were able to significantly reduce their risk of developing artherosclerotic disease, a precursor to heart disease and stroke, and subsequently also reduce their risk of death by roughly 30%. How? Researchers in Connecticut determined that resveratrol preconditions your heart thus providing it with the best protection to avoid cardiac events.

Does your family have a history of cancer? If so, youre likely familiar with colon cancer as, according to the Mayo Clinic, its the most frequently occurring digestive system cancer. Because of its deadly result, researchers across the world continue to search for ways to prevent it. A recent study conducted in France concluded that resveratrol was able to slow down the production of cancerous cells and therefore could be considered an effective anticancer agent. Some of the top natural sources of resveratrol include blueberries, peanuts, grapes, and both red and white wines.

Vision is arguably the most important of your five senses. Even the slightest vision loss is instantly noticeable. Unfortunately, for most, vision loss is a normal part of aging. Luckily, a study by Missouri researchers has found that resveratrol has the ability to counteract this somewhat common occurrence. How? They discovered that resveratrol has the ability to regulate angiogenesis, thereby preventing the abnormal growth of blood vessels that are damaging to eyesight. Other eye-friendly foods to consider include omega-3 fatty fish, as well as foods rich in beta-carotene, vitamin C, and vitamin E.

Do you believe your testosterone needs a boost? As you enter your thirties, its increasingly possible for testosterone to decline. If you think thats happening, visit your physician and ask for a blood test to determine your levels. There are testosterone replacement therapies that could be effective. According to a Korean study conducted on mice, resveratrol may also be an option. The study concluded that blood testosterone concentration was improved by more than 50% following a 28-day period of resveratrol consumption. Even if youre not quite as successful, there are still plenty of other scientifically researched benefits in consuming resveratrol.

Want to get a mental edge? One way is through increased blood flow to your brain. Recently, UK researchers conducted a study of 22 healthy adults and determined that neurological blood flow was increased following resveratrol consumption. Prior to that study, Illinois researchers discovered that mice receiving resveratrol supplementation had better memory function and overall increased mental performance. More research is necessary to determine the extent of its effect, but the good news is that if youre a regular wine drinker, you now have yet another good reason explaining why.

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Working Lung Model with Intact Vasculature Likely to Aid Research, Lung Transplants – Lung Disease News

Researchers at Columbia University have found a way to bioengineer aworking lung a very complex structure with a viable and intactblood vessel network that can support studies of lung cell repair and stem cell transplants, aiding both research into lung diseases and, potentially, the availability of donor lungs.

The team, led by Gordana Vunjak-Novakovic, director of the Laboratory for Stem Cells and Tissue Engineering, recently published itfindings inthe journal Science Advances in a study titled Functional vascularized lung grafts for lung bioengineering.

We developed a radically new approach to bioengineering of the lung, Vunjak-Novakovic, who is also aprofessor of medical sciences at Columbia, said in a news release.

With more than 40 different cell types and a large airway and vasculature surface area, the lung is an incredibly complex organ. It has been a challenge to find ways to promote lung repair to treat advanced lung diseases, the third leading cause of death worldwide.

In contrast toprevious bioengineering projects that required an extensive reconstruction of the lungs vasculature, theteamshowed itis possible to recreate the pulmonary epithelium while preserving its main structural elements, including such supporting such as fibroblasts, myocytes, chondrocytes, and pericytes. The epithelium is tissue that lines the cavities and surfaces of organs and blood vessels.

We reasoned that an ideal lung scaffold would need to have perfusable and healthy vasculature, and so we developed a method that maintains fully functional lung vasculature while we remove defective epithelial lining of the airways and replace it with healthy therapeutic cells, Vunjak-Novakovic said. This ability to selectively treat the pulmonary epithelium is important, as most lung conditions are diseases of the epithelium.

The research team used an ex vivo lung perfusion system (EVLP) in a rodent, and delivered to the lung a mild detergent solution to remove lung tissue-specific cells while protecting the remaining structures and other types of cells.

EVLP works in ways similar to theextracorporeal membrane oxygenation (ECMO) system used to support patients incardiovascular and respiratory failure. EMCObypasses the lungs to provide the body with necessary oxygen and promote gas exchange in an externally controlled system.

Using its system, the team created a lung scaffold with functional bronchial and vascular architecture. These structures were able to support the attachment and growth of human adult and stem cell-derived pulmonary cells.

Researchers think the bioengineered lung model can help with lung repair, andalso help to improve the number of transplantable lungs by makingdonor lungsmore resilient and durable, said Matthew Bacchetta, at associate professor of surgery at the Columbia University Medical Center, and astudyco-author.

The team is nowtesting itsapproach to study lung development and repair in disease, andto develop new targeted therapeutics. They are also focused on developing new imaging-guided lung evaluation strategies for clinical applications.

This research project was supported by a $8.2 million, seven-year grant from the National Institutes of Healththat aims to support research into the mechanisms and treatment of idiopathic pulmonary fibrosis, a serious lung disease.

This is a major step forward in bioengineering lungs, Vunjak-Novakovic said. The creation of de-epithelialized whole lungs with functional vasculature may open new frontiers in lung bioengineering and regenerative medicine.

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Working Lung Model with Intact Vasculature Likely to Aid Research, Lung Transplants - Lung Disease News