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About Genetics | Understanding Genetics

Posted: October 21, 2015 at 1:41 pm

What is a Gene? Look closely at the chromosomes and you'd see that each is made of bundles of looping coils. If you unraveled these coils, you'd have a six-foot long double strand of deoxyribonucleic acid-DNA. A more+ How Do Genes Work? Genes are often called the blueprint for life, because they tell each of your cells what to do and when to do it: be a muscle, make bone, carry nerve signals, and so on. And how do genes orchestrate more+ Why We are Different Biologists use two fancy words to describe the relationship between your genes and your physical traits. The first word is genotype. Your genotype is your genes for a given trait. In most cases, more+ Mutations and Disease DNA is constantly subject to mutations, accidental changes in its code. Mutations can lead to missing or malformed proteins, and that can lead to disease. We all start out our lives with some more+ Genetic Testing Have you ever had your genes tested? Probably not. DNA testing is still pretty limited, although it is becoming more and more common, especially for fetuses and newborns. Many prospective parents, more+ Making Medicines Not long ago, if you were diabetic, the insulin your doctor prescribed would have come from a pig. If you required human growth hormone, it would have come from human cadavers, a source that is more+ New Therapies Many of the worst diseases around are caused by glitches in our genes, and the therapies for these diseases often involve a lifetime of drugs (and their nasty side effects) that help but don't really more+ Ethics The new possibilities created by genetics have brought with them new questions about what is right. An example: genetic testing is, for now, optional. But many medical tests that start out as more+

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Ology Genetics – AMNH

Posted: October 21, 2015 at 1:41 pm

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Home > Genetics | Yale School of Medicine

Posted: October 21, 2015 at 1:41 pm

The information in genomes provides the instruction set for producing each living organism on the planet. While we have a growing understanding of the basic biochemical functions of many of the individual genes in genomes, understanding the complex processes by which this encoded information is read out to orchestrate production of incredibly diverse cell types and organ functions, and how different species use strikingly similar gene sets to nonetheless produce fantastically diverse organismal morphologies with distinct survival and reproductive strategies, comprise many of the deepest questions in all of science. Moreover, we recognize that inherited or acquired variation in DNA sequence and changes in epigenetic states contribute to the causation of virtually every disease that afflicts our species. Spectacular advances in genetic and genomic analysis now provide the tools to answer these fundamental questions.

Members of the Department of Genetics conduct basic research using genetics and genomics of model organisms (yeast, fruit fly, worm, zebrafish, mouse) and humans to understand fundamental mechanisms of biology and disease. Areas of active investigation include genetic and epigenetic regulation of development, molecular genetics, genomics and cell biology of stem cells, the biochemistry of micro RNA production and their regulation of gene expression, and genetic and genomic analysis of diseases in model systems and humans including cancer, cardiovascular and kidney disease, neurodegeneration and regeneration, and neuropsychiatric disease. Members of the Department have also been at the forefront of technology development in the use of new methods for genetic analysis, including new methods for engineering mutations as well as new methods for production and analysis of large genomic data sets.

The Department sponsors a graduate program leading to the PhD in the areas of molecular genetics and genomics, development, and stem cell biology. Admission to the Graduate Program is through the Combined Programs in Biological and Biomedical Sciences (BBS).

In addition to these basic science efforts, the Department is also responsible for providing clinical care in Medical Genetics in the Yale New Haven Health System. Clinical genetics services include inpatient consultation and care, general, subspecialty, cancer and prenatal genetics clinics, and clinical laboratories for cytogenetics, DNA diagnostics, and biochemical diagnostics. The Department sponsors a Medical Genetics Residency program leading to certification by the American Board of Medical Genetics. Admission to the Genetics Residency is directly through the Department.

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Genetics News – Genetics Science, Genetics Technology, Genetics

Posted: October 21, 2015 at 1:41 pm

Last update 23andMe returns with FDA-approved genetic health tests, 9 hours ago

Genetic testing company 23andMe is reintroducing some health screening tools that federal regulators forced off the market more than two years ago, due to concerns about their accuracy and interpretation by customers.

Genetic ancestry, as well as facial characteristics, may play an important part in who we select as mates, according to an analysis from UC San Francisco, Microsoft Research, Harvard, UC Berkeley and Tel Aviv University.

(Medical Xpress)A large team of researchers affiliated with multiple institutions in several European countries has found new genetic variants that put heavy drinkers at higher risk of developing cirrhosis of the liver. ...

Researchers at King's College London have identified a new gene linked to nerve function, which could provide a treatment target for 'switching off' the gene in people with neurodegenerative diseases such as Parkinson's disease.

Never before have scientists been able to make scores of simultaneous genetic edits to an organism's genome. But now, in a landmark study by George Church and his team at the Wyss Institute for Biologically Inspired Engineering ...

Eczema - an itchy dry-skin condition - affects an estimated one in five children and one in 12 adults in the UK. Genes play an important role in determining how likely we are to develop eczema but the majority of the genes ...

Genes involved in schizophrenia and obesity have been highlighted in a new UCL study, which could lead to a better understanding of the DNA variants which affect risk of these conditions and aid the development of improved ...

We've known for years that the Huntingtin protein (Htt) is responsible for Huntington's disease, a neurodegenerative disorder that diminishes a person's mental and physical abilities.

The proposed Regulation on In Vitro Diagnostic Medical Devices (IVDs) negotiations, currently at the stage of tripartite negotiations between the Council (representing Member State governments), the European Parliament, and ...

Using two complementary analytical approaches, scientists at Whitehead Institute and Broad Institute of MIT and Harvard have for the first time identified the universe of genes in the human genome essential for the survival ...

A coalition of leukemia researchers led by scientists from UC San Francisco has discovered surprising genetic diversity in juvenile myelomonocytic leukemia (JMML), a rare but aggressive childhood blood cancer.

In the kidney, injured cells can be kicked into reparative mode by a gene called Sox9, according to a new paper published in Cell Reports.

University of Otago researchers working with zebrafish have published a study providing new insights into the causes of the congenital heart defects associated with a rare developmental disorder.

The team behind the Deciphering Developmental Disorders (DDD) Study, one of the world's largest nationwide rare disease genome-wide sequencing initiatives, have developed a novel computational approach to identify genetic ...

The whimsically named sonic hedgehog gene, best known for controlling embryonic development, also maintains the normal physiological state and repair process of an adult healthy lung, if damaged, according to new research ...

A research group at Tohoku Medical Megabank Organization (ToMMo) has successfully constructed a Japanese population reference panel (1KJPN), from the genome information of 1,070 individuals who had participated in the cohort ...

Walt Whitman's famous line, "I am large, I contain multitudes," has gained a new level of biological relevance.

Research indicates for the first time that mutations within the DNA sequence of mitochondria impact on the energy producing capacity of these cells, with significant effects on fertility and life expectancy - and remarkably ...

A new test detects virtually any virus that infects people and animals, according to research at Washington University School of Medicine in St. Louis, where the technology was developed.

An international team of scientists from the 1000 Genomes Project Consortium has created the world's largest catalog of genomic differences among humans, providing researchers with powerful clues to help them establish why ...

Scientists have calculated more precise measurements of heritabilitythe influence of underlying genesin nine autoimmune diseases that begin in childhood. The research may strengthen researchers' abilities to better ...

Published today in Nature, the findings detail a new gene locus that can explain why, in communities where everyone is constantly exposed to malaria, some children develop severe malaria and others don't. Now, researchers ...

In recent years, University of Utah biologists showed that when wild-type mice compete in seminatural "mouse barns" for food, territory and mates, they can suffer health problems not revealed by conventional toxicity tests ...

An international study of nearly 70,000 women has identified more than forty regions of the human genome that are involved in governing at what age a woman goes through the menopause. The study, led by scientists at the Universities ...

Cells of multicellular organisms contain identical genetic material (the genome) yet can have drastic differences in their structural arrangements and functions. This variation of the distinct cell types comes from the differential ...

Using a genome-wide association study, EPFL scientists have identified subtle genetic changes that can cause substantial differences to how we fight viral infections.

Mitochondria are not only the power plants of our cells, these tiny structures also play a central role in our physiology. Furthermore, by enabling flexible physiological responses to new environments, mitochondria have helped ...

A genetic variant near the KLF14 gene regulates hundreds of genes that govern how and where women's bodies store fat, which affects their risk of developing Type 2 diabetes, according to research presented at the American ...

Progeria, a premature aging disease, is the research focus of Roland Foisner's team at the Max F. Perutz Laboratories of the University of Vienna and the Medical University of Vienna. Children suffering from progeria die ...

Tourists spending a recuperative holiday on the Italian coast may be envious of the regenerative abilities of locally found flatworm Macrostomum lignano. Named for its discovery near the Italian beach town of Lignano Sabbiadoro, ...

Some research has suggested that omega-3 fatty acids, abundant in fish oils, can relieve inflammation in Crohn's disease. But a new study using software developed by Duke scientists hints that we should be paying closer attention ...

A 'gene signature' that could be used to predict the onset of diseases, such as Alzheimer's, years in advance has been developed in research published in the open access journal Genome Biology.

An international team of scientists led from Sweden's Karolinska Institutet has for the first time mapped all the genes that are activated in the first few days of a fertil
ized human egg. The study, which is being published ...

A single stem cell has the potential to generate an animal made of millions of different types of cells. Some cancers contain stem-like but abnormal cells that can act like mini factories to rapidly churn out not only more ...

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Department of Genetics || University of Pennsylvania

Posted: October 21, 2015 at 1:41 pm

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Ethics of Stem Cell Research (Stanford Encyclopedia of …

Posted: October 21, 2015 at 7:42 am

The potential therapeutic benefits of HESC research provide strong grounds in favor of the research. If looked at from a strictly consequentialist perspective, it's almost certainly the case that the potential health benefits from the research outweigh the loss of embryos involved and whatever suffering results from that loss for persons who want to protect embryos. However, most of those who oppose the research argue that the constraints against killing innocent persons to promote social utility apply to human embryos. Thus, as long as we accept non-consequentialist constraints on killing persons, those supporting HESC research must respond to the claim that those constraints apply to human embryos.

In its most basic form, the central argument supporting the claim that it is unethical to destroy human embryos goes as follows: It is morally impermissible to intentionally kill innocent human beings; the human embryo is an innocent human being; therefore it is morally impermissible to intentionally kill the human embryo. It is worth noting that this argument, if sound, would not suffice to show that all or even most HESC research is impermissible, since most investigators engaged in HESC research do not participate in the derivation of HESCs but instead use cell lines that researchers who performed the derivation have made available. To show that researchers who use but do not derive HESCs participate in an immoral activity, one would further need to establish their complicity in the destruction of embryos. We will consider this issue in section 2. But for the moment, let us address the argument that it is unethical to destroy human embryos.

A premise of the argument against killing embryos is that human embryos are human beings. The issue of when a human being begins to exist is, however, a contested one. The standard view of those who oppose HESC research is that a human being begins to exist with the emergence of the one-cell zygote at fertilization. At this stage, human embryos are said to be whole living member[s] of the species homo sapiens [which] possess the epigenetic primordia for self-directed growth into adulthood, with their determinateness and identity fully intact (George & Gomez-Lobo 2002, 258). This view is sometimes challenged on the grounds that monozygotic twinning is possible until around days 1415 of an embryo's development (Smith & Brogaard 2003). An individual who is an identical twin cannot be numerically identical to the one-cell zygote, since both twins bear the same relationship to the zygote, and numerical identity must satisfy transitivity. That is, if the zygote, A, divides into two genetically identical cell groups that give rise to identical twins B and C, B and C cannot be the same individual as A because they are not numerically identical with each other. This shows that not all persons can correctly assert that they began their life as a zygote. However, it does not follow that the zygote is not a human being, or that it has not individuated. This would follow only if one held that a condition of an entity's status as an individual human being is that it be impossible for it to cease to exist by dividing into two or more entities. But this seems implausible. Consider cases in which we imagine adult humans undergoing fission (for example, along the lines of Parfit's thought experiments, where each half of the brain is implanted into a different body) (Parfit 1984). The prospect of our going out of existence through fission does not pose a threat to our current status as distinct human persons. Likewise, one might argue, the fact that a zygote may divide does not create problems for the view that the zygote is a distinct human being.

There are, however, other grounds on which some have sought to reject that the early human embryo is a human being. According to one view, the cells that comprise the early embryo are a bundle of homogeneous cells that exist in the same membrane but do not form a human organism because the cells do not function in a coordinated way to regulate and preserve a single life (Smith & Brogaard 2003, McMahan 2002). While each of the cells is alive, they only become parts of a human organism when there is substantial cell differentiation and coordination, which occurs around day-16 after fertilization. Thus, on this account, disaggregating the cells of the 5-day embryo to derive HESCs does not entail the destruction of a human being.

This account is subject to dispute on empirical grounds. That there is some intercellular coordination in the zygote is revealed by the fact that the development of the early embryo requires that some cells become part of the trophoblast while others become part of the inner cell mass. Without some coordination between the cells, there would be nothing to prevent all cells from differentiating in the same direction (Damschen, Gomez-Lobo and Schonecker 2006). The question remains, though, whether this degree of cellular interaction is sufficient to render the early human embryo a human being. Just how much intercellular coordination must exist for a group of cells to constitute a human organism cannot be resolved by scientific facts about the embryo, but is instead an open metaphysical question (McMahan 2007a).

Suppose that the 5-day human embryo is a human being. On the standard argument against HESC research, membership in the species Homo sapiens confers on the embryo a right not to be killed. This view is grounded in the assumption that human beings have the same moral status (at least with respect to possessing this right) at all stages of their lives.

Some accept that the human embryo is a human being but argue that the human embryo does not have the moral status requisite for a right to life. There is reason to think that species membership is not the property that determines a being's moral status. We have all been presented with the relevant thought experiments, courtesy of Disney, Orwell, Kafka, and countless science fiction works. The results seem clear: we regard mice, pigs, insects, aliens, and so on, as having the moral status of persons in those possible worlds in which they exhibit the psychological and cognitive traits that we normally associate with mature human beings. This suggests that it is some higher-order mental capacity (or capacities) that grounds the right to life. While there is no consensus about the capacities that are necessary for the right to life, some of the capacities that have been proposed include reasoning, self-awareness, and agency (Kuhse & Singer 1992, Tooley 1983, Warren 1973).

The main difficulty for those who appeal to such mental capacities as the touchstone for the right to life is that early human infants lack these capacities, and do so to a greater degree than many of the nonhuman animals that most deem it acceptable to kill (Marquis 2002). This presents a challenge for those who hold that the non-consequentialist constraints on killing human children and adults apply to early human infants. Some reject that these constraints apply to infants, and allow that there may be circumstances where it is permissible to sacrifice infants for the greater good (McMahan 2007b). Others argue that, while infants do not have the intrinsic properties that ground a right to life, we should nonetheless treat them as if they have a right to life in order to promote love and concern towards them, as these attitudes have good consequences for the persons they will become (Benn 1973, Strong 1997).

Some claim that we can reconcile the ascription of a right to life to all humans with the view that higher order mental capacities ground the right to life by distinguishing between two senses of mental capacities: immediately exercisable capacities and basic natural capacities. (George and Gomez-Lobo 2002, 260). According to this view, an individual's immediately exercisable capacity for higher mental functions is the actualization of natural capacities for higher mental functions that exist at the embryonic stage of life. Human embryos have a rational nature, but that nature is not fully realized until individuals are able to exercise their capacity to reason. The difference between these types of capacity is said to be a difference between degrees of development along a continuum. There is merely a quantitative difference between the mental capacities of embryos, fetuses, infants, children, and adults (as well as among infants, children, and adults). And this difference, so the argument runs, cannot justify treating some of these individuals with moral respect while denying it to others.

Given that a human embryo cannot reason at all, the claim that it has a rational nature has struck some as tantamount to asserting that it has the potential to become an individual that can engage in reasoning (Sagan & Singer 2007). But an entity's having this potential does not logically entail that it has the same status as beings that have realized some or all of their potential (Feinberg 1986). Moreover, with the advent of cloning technologies, the range of entities that we can now identify as potential persons arguably creates problems for those who place great moral weight on the embryo's potential. A single somatic cell or HESC can in principle (though not yet in practice) develop into a mature human being under the right conditionsthat is, where the cell's nucleus is transferred into an enucleated egg, the new egg is electrically stimulated to create an embryo, and the embryo is transferred to a woman's uterus and brought to term. If the basis for protecting embryos is that they have the potential to become reasoning beings, then, some argue, we have reason to ascribe a high moral status to the trillions of cells that share this potential and to assist as many of these cells as we reasonably can to realize their potential (Sagan & Singer 2007, Savulescu 1999). Because this is a stance that we can expect nearly everyone to reject, it's not clear that opponents of HESC research can effectively ground their position in the human embryo's potential.

One response to this line of argument has been to claim that embryos possess a kind of potential that somatic cells and HESCs lack. An embryo has potential in the sense of having an active disposition and intrinsic power to develop into a mature human being (Lee & George 2006). An embryo can mature on its own in the absence of interference with its development. A somatic cell, on the other hand, does not have the inherent capacity or disposition to grow into a mature human being. However, some question whether this distinction is viable, especially in the HESC research context. While it is true that somatic cells can realize their potential only with the assistance of outside interventions, an embryo's development also requires that numerous conditions external to it are satisfied. In the case of embryos that are naturally conceived, they must implant, receive nourishment, and avoid exposure to dangerous substances in utero. In the case of spare embryos created through in vitro fertilizationwhich are presently the source of HESCs for researchthe embryos must be thawed and transferred to a willing woman's uterus. Given the role that external factorsincluding technological interventionsplay in an embryo's realizing its potential, one can question whether there is a morally relevant distinction between an embryo's and somatic cell's potential and thus raise doubts about potentiality as a foundation for the right to life (Devolder & Harris 2007).

Some grant that human embryos lack the properties essential to a right to life, but hold that they possess an intrinsic value that calls for a measure of respect and places at least some moral constraints on their use: The life of a single human organism commands respect and protection no matter in what form or shape, because of the complex creative investment it represents and because of our wonder at the divine or evolutionary processes that produce new lives from old ones. (Dworkin l992, 84). There are, however, divergent views about the level of respect embryos command and what limits exist on their use. Some opponents of HESC research hold that the treatment of human embryos as mere research tools always fails to manifest proper respect for them. Other opponents take a less absolutist view. Some, for example, deem embryos less valuable than more mature human beings but argue that the benefits of HESC research are too speculative to warrant the destruction of embryos, and that the benefits might, in any case, be achieved through the use of noncontroversial sources of stem cells (e.g., adult stem cells) (Holm 2003).

Many, if not most, who support the use of human embryos for HESC research would likely agree with opponents of the research that there are some circumstances where the use of human embryos would display a lack of appropriate respect for human life, for example, were they to be offered for consumption to contestants in a reality TV competition or destroyed for the production of cosmetics. But proponents of the research hold that the value of human embryos is not great enough to constrain the pursuit of research that may yield significant therapeutic benefits. Supporters of the research also frequently question whether most opponents of the research are consistent in their ascription of a high value to human embryos, as opponents generally display little concern about the fact that many embryos created for fertility treatment are discarded.

When spare embryos exist after fertility treatment, the individuals for whom the embryos were created typically have the option of storing for them for future reproductive use, donating them to other infertile couples, donating them to research, or discarding them. Some argue that as long as the decision to donate embryos for research is made after the decision to discard them, it is morally permissible to use them in HESC research even if we assume that they have the moral status of persons. The claim takes two different forms. One is that it is morally permissible to kill an individual who is about to be killed by someone else where killing that individual will help others (Curzer, H. 2004). The other is that researchers who derive HESCs from embryos that were slated for destruction do not cause their death. Instead, the decision to discard the embryos causes their death; research just causes the manner of their death (Green 2002).

Both versions of the argument presume that the decision to discard spare embryos prior to the decision to donate them to research entails that donated embryos are doomed to destruction when researchers receive them. There are two arguments one might marshal against this presumption. First, one who wants to donate embryos to research might first elect to discard them only because doing so is a precondition for donating them. There could be cases in which one who chooses the discard option would have donated the embryos to other couples were the research donation option not available. The fact that a decision to discard embryos is made prior to the decision to donate the embryos thus does not establish that the embryos were doomed to destruction before the decision to donate them to research was made. Second, a researcher who receives embryos could choose to rescue them, whether by continuing to store them or by donating them to infertile couples. While this would violate the law, the fact that it is within a researcher's power to prevent the destruction of the embryos he or she receives poses problems for the claim that the decision to discard the embryos dooms them or causes their destruction.

Assume for the sake of argument that it is morally impermissible to destroy human embryos. It does not follow that all research with HESCs is impermissible, as it is sometimes permissible to benefit from moral wrongs. For example, there is nothing objectionable about transplant surgeons and patients benefiting from the organs of murder and drunken driving victims (Robertson 1988). If there are conditions under which a researcher may use HESCs without being complicit in the destruction of embryos, then those who oppose the destruction of embryos could support research with HESCs under certain circumstances.

Researchers using HESCs are clearly implicated in the destruction of embryos where they derive the cells themselves or enlist others to derive the cells. However, most investigators who conduct research with HESCs obtain them from an existing pool of cell lines and play no role in their derivation. One view is that we cannot assign causal or moral responsibility to investigators for the destruction of embryos from which the HESCs they use are derived where their research plans had no effect on whether the original immoral derivation occurred. (Robertson 1999). This view requires qualification. There may be cases in which HESCs are derived for the express purpose of making them widely available to HESC investigators. In such instances, it may be that no individual researcher's plans motivated the derivation of the cells. Nonetheless, one might argue that investigators who use these cells are complicit in the destruction of the embryos from which the cells were derived because they are participants in a research enterprise that creates a demand for HESCs. For these investigators to avoid the charge of complicity in the destruction of embryos, it must be the case that the researchers who derived the HESCs would have performed the derivation in the absence of external demand for the cells (Siegel 2004).

The issue about complicity goes beyond the question of an HESC researcher's role in the destruction of the particular human embryo(s) from which the cells he or she uses are derived. There is a further concern that research with existing HESCs will result in the future destruction of embryos: [I]f this research leads to possible treatments, private investment in such efforts will increase greatly and the demand for many thousands of cell lines with different genetic profiles will be difficult to resist. (U.S. Conference of Catholic Bishops 2001). This objection faces two difficulties. First, it appears to be too sweeping: research with adult stem cells and non-human animal stem cells, as well as general research in genetics, embryology, and cell biology could be implicated, since all of this research might advance our understanding of HESCs and result in increased demand for them. Yet, no one, including those who oppose HESC research, argues that we should not support these areas of research. Second, the claim about future demand for HESCs is speculative. Indeed, current HESC research could ultimately reduce or eliminate demand for the cells by providing insights into cell biology that enable the use of alternative sources of cells (Siegel 2004).

While it might thus be possible for a researcher to use HESCs without being morally responsible for the destruction of human embryos, that does not end the inquiry into complicity. Some argue that agents can be complicit in wrongful acts for which they are not morally responsible. One such form of complicity arises from an association with wrongdoing that symbolizes acquiescence in the wrongdoing (Burtchaell 1989). The failure to take appropriate measures to distance oneself from moral wrongs may give rise to metaphysical guilt, which produces a moral taint and for which shame is the appropriate response (May 1992). The following question thus arises: Assuming it is morally wrongful to destroy human embryos, are HESC researchers who are not morally responsible for the destruction of embryos complicit in the sense of symbolically aligning themselves with a wrongful act?

One response is that a researcher who benefits from the destruction of embryos need not sanction the act any more than the transplant surgeon who uses the organs of a murder or drunken driving victim sanctions the homicidal act (Curzer 2004). But this response is unlikely to be satisfactory to opponents of HESC research. There is arguably an important difference between the transplant case and HESC research insofar as the moral wrong associated with the latter (a) systematically devalues a particular class of human beings and (b) is largely socially accepted and legally permitted. Opponents of HESC research might suggest that the HESC research case is more analogous to the following kind of case: Imagine a society in which the practice of killing members of a particular racial or ethnic group is legally permitted and generally accepted. Suppose that biological materials obtained from these individuals subsequent to their deaths are made available for research uses. Could researchers use these materials while appropriately distancing themselves from the wrongful practice? Arguably, they could not. There is a heightened need to protest moral wrongs where those wrongs are socially and legally accepted. Attempts to benefit from the moral wrong in these circumstances may be incompatible with mounting a proper protest (Siegel 2003).

But even if we assume that HESC researchers cannot avoid the taint of metaphysical guilt, it is not clear that researchers who bear no moral responsibility for the destruction of embryos are morally obligated not to use HESCs. One might argue that there is a prima facie duty to avoid moral taint, but that this duty may be overridden for the sake of a noble cause.

Most HESCs are derived from embryos that were created for infertility treatment but that were in excess of what the infertile individual(s) ultimately needed to achieve a pregnancy. The HESCs derived from these leftover embryos offer investigators a powerful tool for understanding the mechanisms controlling cell differentiation. However, there are scientific and therapeutic reasons not to rely entirely on leftover embryos. From a research standpoint, creating embryos through cloning technologies with cells that are known to have particular genetic mutations would allow researchers to study the underpinnings of genetic diseases in vitro. From a therapeutic standpoint, the HESCs obtained from leftover IVF embryos are not genetically diverse enough to address the problem of immune rejection by recipients of stem cell transplants. (Induced pluripotent stem cells may ultimately prove sufficient for these research and therapeutic ends, since the cells can (a) be selected for specific genetic mutations and (b) provide an exact genetic match for stem cell recipients.) At present, the best way to address the therapeutic problem is through the creation of a public stem cell bank that represents a genetically diverse pool of stem cell lines (Faden et al. 2003, Lott & Savulescu 2007). This kind of stem cell bank would require the creation of embryos from gamete donors who share the same HLA-types (i.e., similar versions of the genes that mediate immune recognition and rejection).

Each of these enterprises has its own set of ethical issues. In the case of research cloning, some raise concerns, for example, that the perfection of cloning techniques for research purposes will enable the pursuit of reproductive cloning, and that efforts to obtain the thousands of eggs required for the production of cloned embryos will result in the exploitation of women who provide the eggs (President's Council on Bioethics 2002, Norsigian 2005). With respect to stem cell banks, it is not practically possible to create a bank of HESCs that will provide a close immunological match for all recipients. This gives rise to the challenge of determining who will have biological access to stem cell therapies. We might construct the bank so that it provides matches for the greatest number of people in the population, gives everyone an equal chance of finding a match, or ensures that all ancestral/ethnic groups are fairly represented in the bank (Faden et al. 2003, Bok, Schill, & Faden 2004, Greene 2006).

There are, however, more general challenges to the creation of embryos for research and therapeutic purposes. Some argue that the creation of embryos for non-reproductive ends is morally problematic, regardless of whether they are created through cloning or in vitro fertilization. There are two related arguments that have been advanced to morally distinguish the creation of embryos for reproductive purposes from the creation of embryos for research and therapeutic purposes. First, each embryo created for procreative purposes is originally viewed as a potential child in the sense that each is a candidate for implantation and development into a mature human. In contrast, embryos created for research or therapies are viewed as mere tools from the outset (Annas, Caplan & Elias 1996, President's Council on Bioethics 2002). Second, while embryos created for research and therapy are produced with the intent to destroy them, the destruction of embryos created for reproduction is a foreseeable but unintended consequence of their creation (FitzPatrick 2003).

One response to the first argument has been to suggest that we could, under certain conditions, view all research embryos as potential children in the relevant sense. If all research embryos were included in a lottery in which some of them were donated to individuals for reproductive purposes, all research embryos would have a chance at developing into mature humans (Devander 2005). Since those who oppose creating embryos for research would likely maintain their opposition in the research embryo lottery case, it is arguably irrelevant whether embryos are viewed as potential children when they are created. Of course, research embryos in the lottery case would be viewed as both potential children and potential research tools. But this is also true in the case of embryos created for reproductive purposes where patients are open to donating spare embryos to research.

As to the second argument, the distinction between intending and merely foreseeing harms is one to which many people attach moral significance, and it is central to the Doctrine of Double Effect. But even if one holds that this is a morally significant distinction, it is not clear that it is felicitous to characterize the destruction of spare embryos as an unintended but foreseeable side-effect of creating embryos for fertility treatment. Fertility clinics do not merely foresee that some embryos will be destroyed, as they choose to offer patients the option of discarding embryos and carry out the disposal of embryos when patients request it. Patients who elect that their embryos be discarded also do not merely foresee the embryos' destruction; their election of that option manifests their intention that the embryos be destroyed. There is thus reason to doubt that there is a moral distinction between creating embryos for research and creating them for reproductive purposes, at least given current fertility clinic practices.

Recent scientific work suggests it is possible to derive gametes from human pluripotent stem cells. Researchers have generated sperm and eggs from mouse ESCs and iPSCs and have used these stem cell-derived gametes to produce offspring (Hayashi 2011; Hayashi 2012). While it may take several years before researchers succeed in deriving gametes from human stem cells, the research holds much promise for basic science and clinical application. For example, the research could provide important insights into the fundamental processes of gamete biology, assist in the understanding of genetic disorders, and provide otherwise infertile individuals a means of creating genetically related children. The ability to derive gametes from human stem cells could also reduce or eliminate the need for egg donors and thus help overcome concerns about exploitation of donors and the risks involved in egg retrieval. Nonetheless, the research gives rise to some controversial issues related to embryos, genetics, and assisted reproductive technologies (D. Mathews et al. 2009).

One issue arises from the fact that some research on stem cell-derived gametes requires the creation of embryos, regardless of whether one is using ESCs or iPSCs. To establish that a particular technique for deriving human gametes from stem cells produces functional sperm and eggs, it is necessary to demonstrate that the cells can produce an embryo. This entails the creation of embryos through in vitro fertilization. Since it would not be safe to implant embryos created during the early stages of the research, the likely disposition of the embryos is that they would be destroyed. In such instances, the research would implicate all of the moral issues surrounding the creation and destruction of embryos for research. However, the creation of embryos for research in this situation would not necessitate the destruction of the embryos, as it does when embryos are created to derive stem cell lines. One could in principle store them indefinitely rather than destroy them. This would still leave one subject to the objection that life is being created for instrumental purposes. But the force of the objection is questionable since it is not clear that this instrumental use is any more objectionable than the routine and widely accepted practice of creating excess IVF embryos in the reproductive context to increase the probability of generating a sufficient number of viable ones to produce a pregnancy.

Further issues emerge with the prospect of being able to produce large quantities of eggs from stem cells. As the capacity to identify disease and non-disease related alleles through preimplantation genetic diagnosis (PGD) expands, the ability to create large numbers of embryos would substantially increase the chances of finding an embryo that possesses most or all of the traits one wishes to select. This would be beneficial in preventing the birth of children with genetic diseases. But matters would become morally contentious if it were possible to select for non-disease characteristics, such as sexual orientation, height, superior intelligence, memory, and musical ability. One common argument against using PGD in this way is that it could devalue the lives of those who do not exhibit the chosen characteristics. Another concern is that employing PGD to select for non-disease traits would fail to acknowledge the giftedness of life by treating children as objects of our design or products of our will or instruments of our ambition rather accepting them as they are given to us (Sandel 2004, 56). There is additionally a concern about advances in genetics heightening inequalities where certain traits confer social and economic advantages and only the well-off have the resources to access the technology (Buchanan 1995). Of course, one can question whether the selection of non-disease traits would in fact lead to devaluing other characteristics, whether it would alter the nature of parental love, or whether it is distinct enough from currently permitted methods of gaining social and economic advantage to justify regulating the practice. Nonetheless, the capacity to produce human stem cell-derived gametes would make these issues more pressing.

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Gene Therapy and Cell Therapy Defined | ASGCT – American …

Posted: October 20, 2015 at 4:44 pm

Gene therapy and cell therapy are overlapping fields of biomedical research with the goals of repairing the direct cause of genetic diseases in the DNA or cellular population, respectively. These powerful strategies are also being focused on modulating specific genes and cell subpopulations in acquired diseases in order to reestablish the normal equilibrium. In many diseases, gene and cell therapy are combined in the development of promising therapies.

In addition, these two fields have helped provide reagents, concepts, and techniques that are elucidating the finer points of gene regulation, stem cell lineage, cell-cell interactions, feedback loops, amplification loops, regenerative capacity, and remodeling.

Gene therapy is defined as a set of strategies that modify the expression of an individuals genes or that correct abnormal genes. Each strategy involves the administration of a specific DNA (or RNA).

Cell therapy is defined as the administration of live whole cells or maturation of a specific cell population in a patient for the treatment of a disease.

Gene therapy: Historically, the discovery of recombinant DNA technology in the 1970s provided the tools to efficiently develop gene therapy. Scientists used these techniques to readily manipulate viral genomes, isolate genes, identify mutations involved in human diseases, characterize and regulate gene expression, and engineer various viral vectors and non-viral vectors. Many vectors, regulatory elements, and means of transfer into animals have been tried. Taken together, the data show that each vector and set of regulatory elements provides specific expression levels and duration of expression. They exhibit an inherent tendency to bind and enter specific types of cells as well as spread into adjacent cells. The effect of the vectors and regulatory elements are able to be reproduced on adjacent genes. The effect also has a predictable survival length in the host. Although the route of administration modulates the immune response to the vector, each vector has a relatively inherent ability, whether low, medium or high, to induce an immune response to the transduced cells and the new gene products.

The development of suitable gene therapy treatments for many genetic diseases and some acquired diseases has encountered many challenges and uncovered new insights into gene interactions and regulation. Further development often involves uncovering basic scientific knowledge of the affected tissues, cells, and genes, as well as redesigning vectors, formulations, and regulatory cassettes for the genes.

While effective long-term treatments for anemias, hemophilia, cystic fibrosis, muscular dystrophy, Gauschers disease, lysosomal storage diseases, cardiovascular diseases, diabetes, and diseases of the bones and joints are elusive today, some success is being observed in the treatment of several types of immunodeficiency diseases, cancer, and eye disorders. Further details on the status of development of gene therapy for specific diseases are summarized here.

Cell therapy: Historically, blood transfusions were the first type of cell therapy and are now considered routine. Bone marrow transplantation has also become a well-established protocol. Bone marrow transplantation is the treatment of choice for many kinds of blood disorders, including anemias, leukemias, lymphomas, and rare immunodeficiency diseases. The key to successful bone marrow transplantation is the identification of a good "immunologically matched" donor, who is usually a close relative, such as a sibling. After finding a good match between the donors and recipients cells, the bone marrow cells of the patient (recipient) are destroyed by chemotherapy or radiation to provide room in the bone marrow for the new cells to reside. After the bone marrow cells from the matched donor are infused, the self-renewing stem cells find their way to the bone marrow and begin to replicate. They also begin to produce cells that mature into the various types of blood cells. Normal numbers of donor-derived blood cells usually appear in the circulation of the patient within a few weeks. Unfortunately, not all patients have a good immunological matched donor. Furthermore, bone marrow grafts may fail to fully repopulate the bone marrow in as many as one third of patients, and the destruction of the host bone marrow can be lethal, particularly in very ill patients. These requirements and risks restrict the utility of bone marrow transplantation to some patients.

Cell therapy is expanding its repertoire of cell types for administration. Cell therapy treatment strategies include isolation and transfer of specific stem cell populations, administration of effector cells, induction of mature cells to become pluripotent cells, and reprogramming of mature cells. Administration of large numbers of effector cells has benefited cancer patients, transplant patients with unresolved infections, and patients with chemically destroyed stem cells in the eye. For example, a few transplant patients cant resolve adenovirus and cytomegalovirus infections. A recent phase I trial administered a large number of T cells that could kill virally-infected cells to these patients. Many of these patients resolved their infections and retained immunity against these viruses. As a second example, chemical exposure can damage or cause atrophy of the limbal epithelial stem cells of the eye. Their death causes pain, light sensitivity, and cloudy vision. Transplantation of limbal epithelial stem cells for treatment of this deficiency is the first cell therapy for ocular diseases in clinical practice.

Several diseases benefit most from treatments that combine the technologies of gene and cell therapy. For example, some patients have a severe combined immunodeficiency disease (SCID) but unfortunately, do not have a suitable donor of bone marrow. Scientists have identified that patients with SCID are deficient in adenosine deaminase gene (ADA-SCID), or the common gamma chain located on the X chromosome (X-linked SCID). Several dozen patients have been treated with a combined gene and cell therapy approach. Each individuals hematopoietic stem cells were treated with a viral vector that expressed a copy of the relevant normal gene. After selection and expansion, these corrected stem cells were returned to the patients. Many patients improved and required less exogenous enzymes. However, some serious adverse events did occur and their incidence is prompting development of theoretically safer vectors and protocols. The combined approach also is pursued in several cancer therapies.

Further information on the progress and status of gene therapy and cell therapy on various diseases is listed here.

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Novartis Pumps $15M Into Israeli Stem Cell Research Firm …

Posted: October 20, 2015 at 12:46 am

The Swiss drug maker Novartis will invest an extra $15 million in Gamida Cell, an Israeli developer of stem cell therapies, Gamida said.

Novartis last year invested $35 million in the company for a 15 percent stake, the Tachles Jewish weekly of Switzerland reported this week. The deal could reach $600 million if Novartis exercises a buyout option that expires in 2016.

The $15 million investment will be used to advance Gamida Cells clinical programs, including the development of an experimental treatment for patients with high risk hematological malignancies, or blood cancers such as leukemia and lymphoma and sickle cell disease.

Gamida plans to initiate a Phase III clinical trial with NiCord in mid-2016, according to Reuters.

Novartis will not have rights or options to Gamida Cell products or technology under the terms of the agreement.

Other Gamida shareholders include Israeli firms that have been the subjects of politically motivated divestment by European business, including Elbit Imaging and Teva Pharmaceutical Industries.

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Home – Vermont Regenerative Medicine

Posted: October 19, 2015 at 5:51 pm

ORTHOPAEDIC MEDICINE SPECIALTIES FOR PAIN TREATMENT Orthopaedic medicine is a specialty devoted to the evaluation, diagnosis and non-operative treatment for pain caused by musculoskeletal diseases to aid in pain management. Diagnostic modalities include a comprehensive history, a detailed and specific physical examination, radiologic evaluations and local anesthetic blocks for pain treatment. Therapeutic modalities for pain management encompass manipulations, corticosteroid or proliferant injections with and without fluoroscopic guidance, therapeutic exercise and use of pharmaceutical, nutriceutical, herbal and/or homeopathic based pain treatment.

The evolution began in 1741 when Nicholas Andre, at that time a Professor of Medicine at the University of Paris, coined the word orthopaedic. He published a book with the same title. The etymology of orthopaedic is based on two greek roots: orthos and paedia which translate to straight and rearing of children respectively. His illustration of a staff that is used to straighten a growing tree is known world wide.

For more than two centuries orthopaedists were physicians or surgeons concerned with musculoskeletal deformities: scoliosis, infections of bones and joints, poliomyelitis and congenital defects such as Erbs palsy, clubfoot and hip dislocations. Until the 20th century most orthopaedic treatments were manipulations and mechanical support with braces and plaster casts.

The American Orthopaedic Association was founded in 1887. The separation of orthopaedic surgery from general surgery took place in 1934 with the establishment of a separate board. According to the late Dr. Cyriax, orthopaedic medicine was established in 1929. The American Association of Orthopaedic Medicine was founded in 1982.

The accumulation of knowledge remains constant. The evolution of pain management continues.

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Curriculum Index – University of Utah

Posted: October 19, 2015 at 5:51 pm

The New Science of Addiction Bioethics and the New Science of Addiction The New Science of Addiction Comparing Brain Images The New Science of Addiction Exploring the New Science of Addiction The New Science of Addiction Jumpin' the Gap The New Science of Addiction Pom-Pom Potential The New Science of Addiction What's the Risk? The New Science of Addiction Worksheet for Drugs of Abuse The New Science of Addiction Worksheet for Mouse Party The New Science of Addiction Worksheet for PI: Pedigree Investigator Astrobiology Aterra 4 Explorer Astrobiology Extremophile Cards Amazing Cells Build-A-Membrane Amazing Cells Coffee to Carbon Amazing Cells Dropping Signals Worksheet Amazing Cells Example of Cell Communication Amazing Cells Inside A Cell Worksheet Amazing Cells Pathways With Friends Amazing Cells When Cells Don't Communicate Cloning Concept Maps on Cloning Cloning Legislation on Cloning Cloning Let's Clone a Mouse, Mouse, Mouse Cloning You've Come a Long Way Dolly Epigenetics DNA & Histone Model Epigenetics Epigenetics Science Talk Epigenetics Your Environment, Your Epigenome Evolution: Variation + Selection & Time Geologic Time in 92 Days Evolution: Variation + Selection & Time Knowledge Quiz Evolution: Variation + Selection & Time Misconception Quiz Evolution: Variation + Selection & Time Reproductive Strategies Family Health History Pick the Risk: The Polygenic Pedigree Challenge Family Health History Reduce Your Risk: A Promotional Campaign Family Health History Risk Continuum Family Health History Using Family History Web Quest Family Health History What's Your Family Health Story? Gene Therapy: Molecular Bandage? Bioethics of Gene Therapy Gene Therapy: Molecular Bandage? How do Viruses Recognize a Target Cell Gene Therapy: Molecular Bandage? Mapping Gene Therapy Concepts Gene Therapy: Molecular Bandage? Patient Education Gene Therapy: Molecular Bandage? Positions, Beliefs and Values Gene Therapy: Molecular Bandage? Vector Selector An Introduction to Heredity and Traits Family Traits and Traditions An Introduction to Heredity and Traits Family Traits Trivia An Introduction to Heredity and Traits Generations of Traits An Introduction to Heredity and Traits Handy Family Tree An Introduction to Heredity and Traits Inventory of My Traits An Introduction to Heredity and Traits Recipe for Traits An Introduction to Heredity and Traits Traits Bingo An Introduction to Heredity and Traits Tree of Genetics Traits Labs Build a Gel Electrophoresis Chamber Labs Colorful Electrophoresis Labs Does Sunscreen Protect My DNA? Labs How to Extract DNA From Anything Living Labs Mystery Yeast Mutation The Human Microbiome Culturing Microbes The Human Microbiome Symbiosis Scramble The Human Microbiome Symbiotic Microbes The Human Microbiome Your Microbial Friends Worksheets Model Earth Using Existing Data Sets Model Earth Water Allocation Molecules of Inheritance Does Sunscreen Protect My DNA? Molecules of Inheritance Find a Gene on the Chromosome Map Molecules of Inheritance Have Your DNA and Eat It Too Molecules of Inheritance Reading DNA Newborn Genetic Screening Genetic Screening of Newborn Infants Pigeon Breeding: Genetics at Work Pigeon Genetics Worksheet Pigeon Breeding: Genetics at Work Pigeonetics Guide Precision Medicine Macromodel of Microarray Precision Medicine Mapping Pharmacogenomics Concepts Precision Medicine SNP Analysis and Pharmacogenetics Precision Medicine Wanna Buy Some Drugs? Stem Cells Go Go Stem Cells Worksheet Stem Cells Stem Cell Tourism Bioethics Stem Cells Stem Cells in Planaria Stem Cells Which Type of Stem Cell Would You Use?

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