DNA Genetic Testing & Analysis - 23andMe

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You are made of cells. And the cells in your body have 23 pairs of chromosomes. Yourchromosomes are made of DNA, which can tell you a lot about you. Explore your 23 pairstoday.

Find out what your 23 pairs of chromosomes can tell you.

Your DNA analysis is performed in US laboratories that are certified to meet CLIAstandardsthe Clinical Laboratory Improvement Amendments of 1988.

A CLIA-certified lab must meet certain quality standards, including qualificationsfor individuals who perform the test and other standards that ensure the accuracyand reliability of results.

We use leading technology to genotype your DNAa custom Illumina HumanOmniExpress-24format chip.

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Provide your saliva sample from home. Mail it back to our lab in the same kit itcame inthe postage is pre-paid.

We bring your genetics to you.

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23andMe was founded in 2006 to help people access, understand and benefitfrom the human genome.

We have more than two million genotyped customers around the world.

In 2015, 23andMe was granted authorization by the US Food and DrugAdministration (FDA) to market the first direct-to-consumer genetic test.

23andMe offers two Personal Genetic Services: Health + Ancestry and Ancestry. Both services require submittinga saliva sample using our saliva collection kit that you send to the lab for analysis.

Our Health + Ancestry Service provides insights on your genetic health risks*, carrier status*, traits,wellness and ancestry. We analyze, compile and distill the information extracted from yourDNA into 75+ reports you can access online and share with family and friends.See full list of reports offered.

Our Ancestry Service helps you understand who you are, where your DNA comes from and your family story. Weanalyze, compile and distill your DNA information into reports on your Ancestry Composition,Maternal & Paternal Haplogroups, NeanderthalAncestry, Your DNA Family and provide a DNA Relatives tool to enable you to connect with relatives who sharesimilar DNA.

*The 23andMe PGS test uses qualitative genotyping to detect clinically relevant variants in the genomic DNA of adultsfrom saliva collected using an FDA-cleared collection device (OrageneDX model OGD-500.001) for the purpose ofreporting and interpreting genetic health risks and reporting carrier status. It is not intended to diagnose anydisease. The relevance of each report may vary based on ethnicity. Each genetic health risk report describes if aperson has variants associated with a higher risk of developing a disease, but does not describe a person's overallrisk of developing the disease. These reports are not intended to tell you anything about your current state ofhealth, or to be used to make medical decisions, including whether or not you should take a medication or how much ofa medication you should take. Our carrier status reports can be used to determine carrier status, but cannotdetermine if you have two copies of any genetic variant. These carrier reports are not intended to tell you anythingabout your risk for developing a disease in the future or anything about the health of your fetus, or your newbornchild's risk of developing a particular disease later in life. For Gaucher Disease Type 1, we provide a single reportthat includes information on both carrier status and genetic health risk.The Parkinson's Disease genetic health risk report (i) is indicated for reporting of the G2019S variant in the LRRK2gene, and the N370S variant in the GBA gene, (ii) describes if a person has variants associated with an increased riskof developing Parkinson's disease, and (iii) is most relevant for people of European, Ashkenazi Jewish, and NorthAfrican Berber descent.

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2 variantsinthe ARMS2 and CFH genes;relevant for European descent

2 variantsinthe SERPINA1 gene;relevant for European descent

2 variantsnearthe HLA-DQA1 and HLA-DQB1 genes;relevant for European descent

2 variantsinthe HFE gene;relevant for European descent

2 variantsinthe F2 and F5 genes;relevant for European descent

1 variantinthe APOE gene;variant found and studied in many ethnicities

2 variantsinthe LRRK2 and GBA genes;relevant for European, Ashkenazi Jewish, North African Berber descent

1 variant in the SACSgene; relevant for French Canadian descent

1 variant in the SLC12A6gene; relevant for French Canadian descent

3 variants in the PKHD1gene

10 variants in the HBBgene; relevant for Cypriot, Greek, Italian, Sardinian descent

1 variant in the BLMgene; relevant for Ashkenazi Jewish descent

3 variants in the ASPAgene; relevant for Ashkenazi Jewish descent

2 variants in the PMM2gene; relevant for Danish descent

28 variants in the CFTRgene; relevant for European, Hispanic/Latino, Ashkenazi Jewish descent

2 variants in the HSD17B4gene

1 variant in the DLDgene; relevant for Ashkenazi Jewish descent

1 variant in the IKBKAPgene; relevant for Ashkenazi Jewish descent

3 variants in the FANCCgene; relevant for Ashkenazi Jewish descent

1 variant in the BCS1Lgene; relevant for Finnish descent

3 variants in the GBAgene; relevant for Ashkenazi Jewish descent

1 variant in the G6PCgene; relevant for Ashkenazi Jewish descent

2 variants in the SLC37A4gene

3 variants in the ALDOBgene; relevant for European descent

3 variants in the LAMB3gene

1 variant in the LRPPRCgene; relevant for French Canadian descent

1 variant in the SGCAgene; relevant for Finnish descent

1 variant in the SGCBgene; relevant for Southern Indiana Amish descent

1 variant in the FKRPgene; relevant for European descent

3 variants in the ACADMgene; relevant for Northern European descent

2 variants in the BCKDHBgene; relevant for Ashkenazi Jewish descent

1 variant in the MCOLN1gene; relevant for Ashkenazi Jewish descent

1 variant in the CLN5gene; relevant for Finnish descent

3 variants in the PPT1gene; relevant for Finnish descent

3 variants in the SMPD1gene; relevant for Ashkenazi Jewish descent

1 variant in the NBNgene; relevant for Eastern European descent

2 variants in the GJB2gene; relevant for Ashkenazi Jewish, European descent

6 variants in the SLC26A4gene

23 variants in the PAHgene; relevant for Northern European descent

1 variant in the GRHPRgene; relevant for European descent

1 variant in the PEX7gene

1 variant in the SLC17A5gene; relevant for Finnish, Swedish descent

1 variant in the HBBgene; relevant for African descent

1 variant in the ALDH3A2gene; relevant for Swedish descent

4 variants in the HEXAgene; relevant for Ashkenazi Jewish, Cajun descent

4 variants in the FAHgene; relevant for French Canadian, Finnish descent

1 variant in the PCDH15gene; relevant for Ashkenazi Jewish descent

1 variant in the CLRN1gene; relevant for Ashkenazi Jewish descent

1 variant in the PEX1gene

when you buy 2+ Ancestry Service kits,savings based on regular price per kit

Health + Ancestry $199

2 variantsinthe ARMS2 and CFH genes;relevant for European descent

2 variantsinthe SERPINA1 gene;relevant for European descent

2 variantsnearthe HLA-DQA1 and HLA-DQB1 genes;relevant for European descent

2 variantsinthe HFE gene;relevant for European descent

2 variantsinthe F2 and F5 genes;relevant for European descent

1 variantinthe APOE gene;variant found and studied in many ethnicities

2 variantsinthe LRRK2 and GBA genes;relevant for European, Ashkenazi Jewish, North African Berber descent

1 variant in the SACSgene; relevant for French Canadian descent

1 variant in the SLC12A6gene; relevant for French Canadian descent

More here:
23andMe - Official Site

Recommendation and review posted by sam

If you or a loved one will be having a bone marrow transplant or donating stem cells, what does it entail? What are the different types of bone marrow transplants and what is the experience like for both the donor and recipient?

A bone marrow transplant is a procedure in which when special cells (called stem cells) are removed from the bone marrow or peripheral blood, filtered and given back either to the same person or to another person.

Since we now derive most stem cells needed from the blood rather than the bone marrow, a bone marrow transplant is now more commonly referred to as stem cell transplant.

Bone marrow is found in larger bones in the body such as the pelvic bones. This bone marrow is the manufacturing site for stem cells. Stem cells are "pluripotential" meaning that the cells are the precursor cells which can evolve into the different types of blood cells, such as white blood cells, red blood cells, and platelets.

If something is wrong with the bone marrow or the production of blood cells is decreased, a person can become very ill or die. In conditions such as aplastic anemia, the bone marrow stops producing blood cells needed for the body. In diseases such as leukemia, the bone marrow produces abnormal blood cells.

The purpose of a bone marrow transplant is thus to replace cells not being produced or replace unhealthy stem cells with healthy ones.

This can be used to treat or even cure the disease.

In addition for leukemias, lymphomas, and aplastic anemia, stem cell transplants are being evaluated for many disorders, ranging from solid tumors to other non-malignant disorders of the bone marrow, to multiple sclerosis.

There are two primary types of bone marrow transplants, autologous and allogeneic transplants.

The Greek prefix "auto" means "self." In an autologous transplant, the donor is the person who will also receive the transplant. This procedure, also known as a "rescue transplant" involves removing your stem cells and freezing them. You then receive high dose chemotherapy followed by infusion of the thawed out frozen stem cells. It may be used to treat leukemias, lymphomas, or multiple myeloma.

The Greek prefix "allo" means "different" or "other." In an allogeneic bone marrow transplant, the donor is another person who has a genetic tissue type similar to the person needing the transplant. Because tissue types are inherited, similar to hair color or eye color, it is more likely that you will find a suitable donor in a family member, especially a sibling. Unfortunately, this occurs only 25 to 30 percent of the time.

If a family member does not match the recipient, the National Marrow Donor Program Registry database can be searched for an unrelated individual whose tissue type is a close match. It is more likely that a donor who comes from the same racial or ethnic group as the recipient will have the same tissue traits.

Learn more about finding a donor for a stem cell transplant.

Bone marrow cells can be obtained in three primary ways. These include:

The majority of stem cell transplants are done using PBSC collected by apheresis (peripheral blood stem cell transplants.) This method appears to provide better results for both the donor and recipient. There still may be situations in which a traditional bone marrow harvest is done.

Donating stem cells or bone marrow is fairly easy. In most cases, a donation is made using circulating stem cells (PBSC) collected by apheresis. First, the donor receives injections of a medication for several days that causes stem cells to move out of the bone marrow and into the blood. For the stem cell collection, the donor is connected to a machine by a needle inserted in the vein (like for donating blood.) Blood is taken from the vein, filtered by the machine to collect the stem cells, then returned back to the donor through a needle in the other arm. There is almost no need for a recovery time with this procedure.

If stem cells are collected by bone marrow harvest (much less likely,) the donor will go to the operating room and while asleep under anesthesia, a needle will be inserted into either the hip or the breastbone to take out some bone marrow. After awakening, there may be some pain where the needle was inserted.

A bone marrow transplant can be a very challenging procedure for the recipient.

The first step is usually receiving high doses of chemotherapy and/or radiation to eliminate whatever bone marrow is present. For example, with leukemia, it is first important to remove all of the abnormal bone marrow cells.

Once a person's original bone marrow is destroyed, the new stem cells are injected intravenously, similar to a blood transfusion. The stem cells then find their way to the bone and start to grow and produce more cells (called engraftment.)

There are many potential complications. The most critical time is usually when the bone marrow is destroyed so that few blood cells remain. Destruction of the bone marrow results in greatly reduced numbers of all of the types of blood cells (pancytopenia.) Without white blood cells there is a serious risk of infection, and infection precautions are used in the hospital (isolation.) Low levels of red blood cells (anemia) often require blood transfusions while waiting for the new stem cells to begin growing. Low levels of platelets (thrombocytopenia) in the blood can lead to internal bleeding.

A common complication affecting 40 to 80 percent of recipients is graft versus host disease. This occurs when white blood cells (T cells) in the donated cells (graft) attack tissues in the recipient (the host,) and can be life-threatening.

An alternative approach referred to as a non-myeloablative bone marrow transplant or "mini-bone marrow transplant" is somewhat different. In this procedure, lower doses of chemotherapy are given that do not completely wipe out or "ablate" the bone marrow as in a typical bone marrow transplant. This approach may be used for someone who is older or otherwise might not tolerate the traditional procedure. In this case, the transplant works differently to treat the disease as well. Instead of replacing the bone marrow, the donated marrow can attack cancerous cells left in the body in a process referred to as "graft versus malignancy."

If you'd like to become a volunteer donor, the process is straightforward and simple. Anyone between the ages of 18 and 60 and in good health can become a donor. There is a form to fill out and a blood sample to give; you can find all the information you need at the National Marrow Donor Program Web site. You can join a donor drive in your area or go to a local Donor Center to have the blood test done.

When a person volunteers to be a donor, his or her particular blood tissue traits, as determined by a special blood test (histocompatibility antigen test,) are recorded in the Registry. This "tissue typing" is different from a person's A, B, or O blood type. The Registry record also contains contact information for the donor, should a tissue type match be made.

Bone marrow transplants can be either autologous (from yourself) or allogeneic (from another person.) Stem cells are obtained either from peripheral blood, a bone marrow harvest or from cord blood that is saved at birth.

For a donor, the process is relatively easy. For the recipient, it can be a long and difficult process, especially when high doses of chemotherapy are needed to eliminate bone marrow. Complications are common and can include infections, bleeding, and graft versus host disease among others.

That said, bone marrow transplants can treat and even cure some diseases which had previously been almost uniformly fatal. While finding a donor was more challenging in the past, the National Marrow Donor Program has expanded such that many people without a compatible family member are now able to have a bone marrow/stem cell transplant.

Sources:

American Society of Clinical Oncology. Cancer.Net. What is a Stem Cell Transplant (Bone Marrow Transplant)? Updated 01/16. http://www.cancer.net/navigating-cancer-care/how-cancer-treated/bone-marrowstem-cell-transplantation/what-stem-cell-transplant-bone-marrow-transplant

U.S. National Library of Medicine. MedlinePlus. Bone Marrow Transplant. Updated 10/03/17. https://medlineplus.gov/ency/article/003009.htm

Read the original post:
bone marrow/stem cell transplant - verywell.com

Recommendation and review posted by sam

By Sara Gottfried MD

Jill, a patient of mine, felt a true physiological need for caffeine, similar to how a diabetic needs insulin. She couldnt imagine life without coffee. The thought of removing it from her daily routine almost caused her to miss out on one of the most important decisions of her life, which was doing The Hormone Reset Diet. In retrospect, she was glad that she didnt [Read More...]

By Sara Gottfried MD

Lets start with an insulin reset! Remember, the seventy- two- hour reset is a simple way to take care of the chronic symptoms that plague you, especially fat gain. Each cycle takes a mere three days to reverse and reset your bodys hormone receptors. Of course, the Hormone Reset is a twenty-one-day program, so as you focus on each reset and tune into the changes that [Read More...]

By Sara Gottfried MD

The patient I am going to describe is unique in her own issues, but her frustration with conventional medicine could be duplicated in my practice many times over.Louisa is a forty-five-year-old teacher and mother of two. After the birth of her children, she was unable to lose the twenty-five pounds she gained and she was experiencing profound fatigue. After [Read More...]

By Sara Gottfried MD

With the release of my newest book Younger, Ive spent a lot of time recently thinking about aging. As a doctor, I not only look at the physiological external effects of aging, such as the wrinkles, hair loss, and weight changes, but also the internal changes: thinning bones, failing memory, rising inflammation, and declining mood. These are very real challenges that [Read More...]

By Sara Gottfried MD

As a woman, youre on ahormonal roller coaster ridemost of your life. My books The Hormone Cure, The Hormone Reset Diet, and Younger were born of my passion to help women,one hormone at a time. I want to help you do that so you can stay looking and feeling great at every age.Hormones are chemical messages, like text messages sent from an endocrine gland [Read More...]

By Sara Gottfried MD

Many women hesitate to bring up the topic of constipation with their doctor. While its common, few women want to talk about it. But constipation is not an issue you want to keep under wraps. When your bowel movements are regular, chances are that your hormonescortisol, estrogen, and thyroidare working at their best.[1] Below are my natural remedies for [Read More...]

By Sara Gottfried MD

I woke up from anesthesia about two months ago, euphoric from the certainty that I made the right choice to undergo a bilateral prophylactic mastectomy for a faulty breast cancer gene called CHEK2. I snapped a quick selfie, unadorned and very raw, in my hospital bed and wanted to share it with you (see photo).Breasts are an important symbol of so many things: [Read More...]

Read the original:
Sara Gottfried MD | At Home in Your Body, At Last

Recommendation and review posted by simmons

INTRODUCTION

Sperm production cannot be stimulated in men who are infertile as a result of primary hypogonadism due to damage to the seminiferous tubules. On the other hand, sperm production can usually be stimulated to a level sufficient to restore fertility in men who are infertile as a result of secondary hypogonadism, ie, due to damage to the pituitary or hypothalamus. Men who have pituitary disease can be treated with gonadotropins, while those with hypothalamic disease can be treated with gonadotropins or gonadotropin-releasing hormone (GnRH). (See "Causes of secondary hypogonadism in males".)

PRETREATMENT EVALUATION

Which patients are likely to respond?The diagnosis of secondary hypogonadism must be firmly established before therapy is begun, since only patients whose infertility is due to this disorder will respond. We recommend treatment with gonadotropins for most men who have secondary hypogonadism due to either hypothalamic or pituitary disease who wish to become fertile (see "Clinical features and diagnosis of male hypogonadism"). Gonadotropin treatment will not increase the sperm count in men who have idiopathic oligospermia, in which a subnormal sperm count is associated with a normal serum testosterone concentration [1].

Several factors enhance the likelihood that the sperm count will be increased, and increased sooner after gonadotropin administration:

Development of hypogonadism after puberty rather than before. In one study, as an example, all six men whose hypogonadism occurred postpubertally experienced an increase in total sperm count from less than one million to above 40 million per ejaculate when treated with human chorionic gonadotropin (hCG) (see 'Initial treatment: hCG' below). In comparison, only one of eight men whose hypogonadism occurred prepubertally (but without cryptorchidism) had a similar response [2].

Partial hypogonadism, rather than complete, as judged by testes that are not as small [3-6], and serum concentrations of follicle-stimulating hormone (FSH), inhibin B, and testosterone that are not as low [7].

Literature review current through:Oct 2017.|This topic last updated:Dec 16, 2015.

View post:
Induction of fertility in men with secondary hypogonadism

Recommendation and review posted by sam

By Amy Orciari Herman

Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM

Menopausal hormone therapy does not put women at increased risk for death, according to long-term follow-up from the Women's Health Initiative (WHI) randomized trials published in JAMA.

In the WHI, nearly 17,000 postmenopausal women with a uterus were randomized to receive either daily conjugated equine estrogens (CEE) plus medroxyprogesterone acetate, or placebo. An additional 11,000 women who'd had a hysterectomy were randomized to CEE alone or placebo.

During 18 years' follow-up which included roughly 57 years of treatment and 1112 years of post-intervention follow-up 27% of the women died. Neither combination hormone therapy nor CEE alone was associated with all-cause mortality during the intervention or post-intervention phase. Findings were similar for cardiovascular and cancer mortality.

An editorialist calls the findings "compelling and reassuring." She concludes: "For women with troubling vasomotor symptoms, premature menopause, or early-onset osteoporosis, hormone therapy appears to be both safe and efficacious."

More here:
Menopausal Hormone Therapy Not Associated with Mortality ...

Recommendation and review posted by sam

Johns Hopkins researchers, working with an international consortium, say they have generated stem cells from skin cells from a person with a severe, early-onset form of Huntingtons disease (HD), and turned them into neurons that degenerate just like those affected by the fatal inherited disorder.

By creating HD in a dish, the researchers say they have taken a major step forward in efforts to better understand what disables and kills the cells in people with HD, and to test the effects of potential drug therapies on cells that are otherwise locked deep in the brain.

Although the autosomal dominant gene mutation responsible for HD was identified in 1993, there is no cure. No treatments are available even to slow its progression.

The research, published in the journal Cell Stem Cell, is the work of a Huntingtons Disease iPSC Consortium, including scientists from the Johns Hopkins University School of Medicine in Baltimore, Cedars-Sinai Medical Center in Los Angeles and the University of California, Irvine, as well as six other groups. The consortium studied several other HD cell lines and control cell lines in order to make sure results were consistent and reproducible in different labs.

The general midlife onset and progressive brain damage of HD are especially cruel, slowly causing jerky, twitch-like movements, lack of muscle control, psychiatric disorders and dementia, and eventually death. In some cases (as in the patient who donated the material for the cells made at Johns Hopkins), the disease can strike earlier, even in childhood.

Having these cells will allow us to screen for therapeutics in a way we havent been able to before in Huntingtons disease, says Christopher A. Ross, M.D., Ph.D., a professor of psychiatry and behavioral sciences, neurology, pharmacology and neuroscience at the Johns Hopkins University School of Medicine and one of the studys lead researchers. For the first time, we will be able to study how drugs work on human HD neurons and hopefully take those findings directly to the clinic.

Ross and his team, as well as other collaborators at Johns Hopkins and Emory University, are already testing small molecules for the ability to block HD iPSC degeneration. These small molecules have the potential to be developed into novel drugs for HD.

The ability to generate from stem cells the same neurons found in Huntingtons disease may also have implications for similar research in other neurodegenerative diseases such as Alzheimers and Parkinsons.

To conduct their experiment, Ross took a skin biopsy from a patient with very early onset HD. When seen by Ross at the HD Center at Hopkins, the patient was just seven years old. She had a very severe form of the disease, which rarely appears in childhood, and of the mutation that causes it. Using cells from a patient with a more rapidly progressing form of the disease gave Ross team the best tools with which to replicate HD in a way that is applicable to patients with all forms of HD.

Her skin cells were grown in culture and then reprogrammed by the lab of Hongjun Song, Ph.D., a professor at Johns Hopkins Institute for Cell Engineering, into induced pluripotent stem cells. A second cell line was generated in an identical fashion in Dr. Rosss lab from someone without HD. Simultaneously, other HD and control iPS cell lines were generated as part of the NINDS funded HD iPS cell consortium.

Scientists at Johns Hopkins and other consortium labs converted those cells into generic neurons and then into medium spiny neurons, a process that took three months. What they found was that the medium spiny neurons deriving from HD cells behaved just as they expected medium spiny neurons from an HD patient would. They showed rapid degeneration when cultured in the lab using basic culture medium without extensive supporting nutrients. By contrast, control cell lines did not show neuronal degeneration.

These HD cells acted just as we were hoping, says Ross, director of the Baltimore Huntington's Disease Center. A lot of people said, Youll never be able to get a model in a dish of a human neurodegenerative disease like this. Now, we have them where we can really study and manipulate them, and try to cure them of this horrible disease. The fact that we are able to do this at all still amazes us.

Specifically, the damage caused by HD is due to a mutation in the huntingtin gene (HTT), which leads to the production of an abnormal and toxic version of the huntingtin protein. Although all of the cells in a person with HD contain the mutation, HD mainly targets the medium spiny neurons in the striatum, part of the brains basal ganglia that coordinates movement, thought and emotion. The ability to work directly with human medium spiny neurons is the best way, researchers believe, to determine why these specific cells are susceptible to cell stress and degeneration and, in turn, to help find a way to halt progression of HD.

Much HD research is conducted in mice. And while mouse models have been helpful in understanding some aspects of the disease, researchers say nothing compares with being able to study actual human neurons affected by HD.

For years, scientists have been excited about the prospect of making breakthroughs in curing disease through the use of stem cells, which have the remarkable potential to develop into many different cell types. In the form of embryonic stem cells, they do so naturally during gestation and early life. In recent years, researchers have been able to produce induced pluripotent stem cells (iPSCs), which are adult cells (like the skin cells used in Rosss experiments) that have been genetically reprogrammed back to the most primitive state. In this state, under the right circumstances, they can then develop into most or all of the 200 cell types in the human body.

The other members of the research consortium include the University of Wisconsin School of Medicine, Massachusetts General Hospital and Harvard Medical School, the University of California, San Francisco, Cardiff University the Universita degli Studi diMilano and the CHDI Foundation.

Primary support for this research came from an American Recovery and Reinvestment Act (ARRA) grant (RC2-NS069422) from the National Institutes of Healths National Institute of Neurological Disorders and Stroke and a grant from the CHDI Foundation, Inc.

Other Johns Hopkins researchers involved in this study include Sergey Akimov, Ph.D.; Nicolas Arbez, Ph.D.; Tarja Juopperi, D.V.M., Ph.D.; Tamara Ratovitski; Jason H. Chiang; Woon Roung Kim; Eka Chighladze, M.S., M.B.A.; Chun Zhong; Georgia Makri; Robert N. Cole; Russell L. Margolis, M.D.; and Guoli Ming, M.D., Ph.D.

More:
Turning Skin Cells Into Brain Cells - 06/28/2012

Recommendation and review posted by simmons

The acronyms might not be quite as catchy as CRISPR, but what new genetic tools dubbed REPAIR and ABE lack in whimsy they promise to make up in utility. These advances, unveiled last week, solve two of the problems hobbling CRISPR, the revolutionary genome-editing technique: that its idea of editing is often like 1,000 monkeys editing a Word document, and that making permanent changes to DNA might not be the best approach.

Together, the discoveries, described in separate studies, show that five years after scientists demonstrated that CRISPR can edit DNA, bioengineers are still racing to develop the most efficient, precise, versatile and therefore lucrative genome-editing tools possible.

One reason these are so exciting is, they show the CRISPR toolbox is still growing, said chemical engineer Gene Yeo of the University of California San Diego. There are going to be a lot more, and its not going to stop anytime soon. His lab has been working on one of the CRISPR advances but was not involved in either of the two new studies; its personally frustrating to get beaten, he added.

One discovery, led by biochemist David Liu of Harvard University, extends his 2016 invention of a way to change a single DNA letter, or base, on the 3-billion-letter-long human genome. Classic CRISPR cuts DNA with a molecular scissors and leaves the cell to repair the breach willy-nilly, introducing the problem of 1,000 monkeys editing away. In contrast, Lius base editor replaces the molecular scissors with something like a pencil wielded by an expert forger: It is an enzyme that literally rearranges atoms, cleanly and without collateral damage that the cell needs to fix.

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As in classic CRISPR, this version finds its way to a target on the genome via a molecule that acts like a bloodhound. Attached to the bloodhound is the atom-rearranger, which in Lius 2016 version turned the DNA letter G into A. Thousands of genetic diseases arise because a gene has a G where it should have an A, so the edit might one day treat or prevent them.

But other inherited disorders need different alphabetical magic. Thats what Liu, postdoctoral fellows Nicole Gaudelli and Alexis Komor, and their colleagues report in a paper in Nature: Their new ABE (adenine base editor) can turn A into G. Attached to CRISPRs bloodhound molecule, ABE works at virtually any target site in genomic DNA, Liu said.

In tests so far, it changed DNA in more of the lab-grown human cells that it was slipped into than standard CRISPR.

About half of the 32,000 known disease-causing, single-letter mutations have one of the misspellings that ABE can fix, Liu said. They include sickle cell, Tay-Sachs, and cystic fibrosis, raising hopes that ABE could be used to treat these diseases, or (in early embryos) prevent them. In tests of cells growing in lab dishes, ABE reversed the mutation that causes hereditary hemochromatosis in about 30 percent of the cells, and changed another gene into a form that prevents sickle cell disease even in people who have its disease-causing mutation.

As with all forms of CRISPR, before ABE helps any patients, scientists will have to test whether its safe and effective. But having the molecular machine is a good start, said Liu, a cofounder of the CRISPR company Editas Medicine Inc., based in Cambridge. He and his colleagues have filed for patents on ABE.

Harvard biologist George Church, who tied for first in the race to make CRISPR work in human cells, called base editing especially interesting. Changing a single DNA letter, he said, means fewer worries about the editing enzyme [in classic CRISPR] later going rogue or silent. He also expects that crops with a single base change will not be designated as transgenic, reducing regulatory barriers to commercialization.

In a separate study, CRISPR pioneer Feng Zhang of Cambridges Broad Institute discovered along with his colleagues a new version of CRISPR that can edit RNA, DNAs friskier cousin. While DNA mostly sits sedately in cells and issues orders to make proteins that keep life living, RNA zips around the cell carrying out those orders, and then disappears. That makes RNA a tantalizing target: By editing the errant orders (RNA) rather than their issuer (DNA), scientists might be able to make temporary, reversible genetic edits, rather than CRISPRs permanent ones.

Editing DNA is hard to reverse, but once you stop providing the RNA-editing system, the changes will disappear over time, said Zhang, also a cofounder of Editas. That might make it possible to treat conditions where you dont need a permanent edit, such as when the immune system is in overdrive and causing inflammation.

To create what Zhang and his colleagues call REPAIR (RNA editing for programmable A to I [G] replacement), they fused an enzyme that binds to RNA with one that changes the RNA letter A (adenosine) to inosine, a molecule similar to the RNA letter G (guanosine), they report in Science.

In tests on human cells growing in the lab, REPAIR corrected misspellings in the RNA that was made by disease-causing DNA in this case, Fanconi anemia, an inherited and devastating bone marrow disease, or nephrogenic diabetes insipidus, a serious inborn kidney disease.

The furious race to improve CRISPR, via ABE or REPAIR or whatever comes next, Church said, is a reminder of how far CRISPR is from precise genome-editing in humans.

Excerpt from:
CRISPR gene editing gets new tools, and acronyms

Recommendation and review posted by simmons

by Michael G. Darwin, Chana de Wolf, and Aschwin de Wolf

Note: A PDF version of this article with images and appendixes is available here.

A Literal Death Sentence

One unpleasant issue in cryonics is the hostile wife phenomenon. The authors of this article know of a number of high profile cryonicists who need to hide their cryonics activities from their wives and ex-high profile cryonicists who had to choose between cryonics and their relationship. We also know of men who would like to make cryonics arrangements but have not been able to do so because of resistance from their wives or girlfriends. In such cases, the female partner can be described as nothing less than hostile toward cryonics. As a result, these men face certain death as a consequence of their partners hostility.

While it is not unusual for any two people to have differing points of view regarding cryonics, men are more interested in making cryonics arrangements. A recent membership update from the Alcor Life Extension Foundation reports that 667 males and 198 females have made cryonics arrangements. Although no formal data are available, it is common knowledge that a substantial number of these female cryonicists signed up after being persuaded by their husbands or boyfriends. For whatever reason, males are more interested in cryonics than females. These issues raise an obvious question: are women more hostile to cryonics than men?

There is no direct answer to this question since the requisite data have not been collected. However, both the gravity and magnitude of the problem, as we are about to detail, suggests this as a fertile, if not urgent, area for future research. One consequence of men being more interested in cryonics than women is that heterosexual men are more often faced with hostile wives and girlfriends than the other way round. While this may sound alarming, such disagreements can easily be overcome if the love and trust in a relationship is strong enough that the disagreeing party can still cede the right to make (and keep) cryonics arrangements to the other individual. However, even formerly amenable wives can become increasingly hostile, frequently in accordance with their husbands increasingly personal and active involvement in cryonics.

An Historical Overview

From its inception in 1964, cryonics has been known to frequently produce intense hostility from spouses who are not cryonicists. While this phenomenon, as previously noted, is mostly confined to hostility from wives or girlfriends, rather than husbands or boyfriends of cryonicists, there are exceptions. One of us (Darwin) knows of two divorces resulting from hostile husbands, and several cases where the husband has delivered an ultimatum to his wife to either cease involvement with cryonics or face dissolution of the marriage(1). An example of male spousal hostility to cryonics is the case of a pioneering female cryonicist who first signed up at the start of the cryonics movement in 1964 and who had a 30+ year history of intense cryonics activism, including serving as an Officer or Director of two early cryonics organizations. When she became incapacitated by Alzheimers disease, her husband, (who had long been unhappy with her involvement in cryonics) cancelled her cryonics and cryonics funding arrangements, and declined to allow her to be cryopreserved. Another co-author (Aschwin de Wolf) was involved in helping out in a situation where the ex-husband of a female friend would not approve cryonics arrangements for his minor children, despite a strong desire from the mother and the children to make such arrangements.

Dating this phenomenon to the earliest days of cryonics is not difficult. In 1968 Robert Ettinger, the father of the cryonics movement, wrote:

This is not a hobby or conversation piece: it is the principal activity of this phase of our lives; it is the struggle for survival. Drive a used car if the cost of a new one interferes. Divorce your wife if she will not cooperate. Save your money; get another job and save more money. Sometimes a fool will blunder through, but dont count on it. The universe has no malice, but neither has it mercy, and a miss is as good as a mile.

It is notable, and by no means accidental, that Ettinger uses the words, Divorce your wife if she will not cooperate, as opposed to divorce your husband or the gender neutral divorce your spouse. Notwithstanding the few cases of hostile husbands or boyfriends, the phenomenon of the hostile spouse is almost exclusively a female phenomenon. There is no reason to be surprised about the fact that only one partner in a relationship has made cryonics arrangements. What needs explanation is why partners are actively hostile to the other partners cryonics arrangements or activities.

Over the 40 years of his active involvement, one of us (Darwin) has kept a log of the instances where, in his personal experience, hostile spouses or girlfriends have prevented, reduced or reversed the involvement of their male partner in cryonics. This list (see appendix) is restricted to situations where Darwin had direct knowledge of the conflict and was an Officer, Director or employee of the cryonics organization under whose auspices the incident took place. This log spans the years 1978 to 1986, an 8 year period. The motivating events for keeping such a log were the intense hostility he experienced from Diane Henderson, the wife of Curtis Henderson, then President of the Cryonics Society of New York (CSNY)) during visits he made to CSNY as a teenager. While this hostility was to cryonics in general, it had as its focus anyone perceived to be facilitating her husbands continued involvement in cryonics. The primary targets were thus Henderson, Darwin and the Vice President of CSNY Gillian Cummings (nee Beverly Greenburg). Curtis Henderson has stated that he believes this antipathy materially contributed to the death of Gillian Cummings in 1972:

Because the (Cryo-Span) facility was not heated and it was bitterly cold at night in the winter on Long Island, Beverly (Gillian) used to spend the night at my home in Sayville on the couch in the CSNY office. Dianes increasingly hostility to Beverly, and to anything or anyone involved in cryonics, put an end to that. A few days before Beverlys death the situation between Diane and I had reached a breaking point. She demanded that I cease involvement in cryonics and close the facility. When I refused, she took our son and went to stay at her mothers home. This is a hard thing to bear and the one thing I didnt want to do was to further antagonize Diane or provide any basis for claims of infidelity in the event she returned home and found Beverly in the house. So, that night I told Beverly she could not spend the night at 9 Holmes Court. Instead, she spent the night in the unheated facility. She was found dead the next day, her keys in her car ignition and the gas tank empty. She was in the habit of running the engine briefly in the closed storage bay to warm up the car enough so she could get back to sleep. She probably dozed off and left the engine running. The only things I can say about that incident is that it has left me with gnawing guilt and a great deal of anger. It was senseless; senseless and irrational.(2)

The second incident that influenced Darwin to keep this record was an experience he had during the start-up of the Indiana cryonics organization the Institute for Advanced Biological Studies (IABS). Desperate for competent and energetic members and administrators, both Darwin and IABS President Steve Bridge experienced intense frustration when two enthusiastic and talented young men withdrew from involvement in IABS and cryonics because of the extreme hostility to cryonics on the part of their wives. This was one of many such incidents, but these two were especially significant because they deprived the nascent cryonics organization of a skilled businessman and potential leader, and of a competent engineer who had assisted with the fabrication of perfusion and cool-down equipment.

While neither objective nor rigorously scientific, the results of Darwins log are nevertheless instructive. The results are summarized in Table 1 (see appendix).

The 91 people listed in this table include 3 whose deaths are directly attributable to hostility or active intervention on the part of women. This does not include the many instances since 1987 where wives, mothers, sisters, or female business partners have materially interfered with a patients cryopreservation(3) or actually caused the patient not to be cryopreserved or removed from cryopreservation(4). Nor does it reflect the doubtless many more cases where we had no idea that:

The wifes hostility/objections/commands/threats prevented the husband from inquiring in the first place.

The wifes hostility/objections/commands/threats prevented the husband from signing up but no one knew it.

The wifes hostility/objections/commands/threats prevented the husband who was a member from volunteering, attending meetings, or otherwise becoming more involved, including standing for directorship positions and participating in research.

The wifes hostility/objections/commands/threats resulted in lapse of membership.

Prospective patients did not inquire because they knew the wifes hostility/objections/commands/threats would cause loss of support, emotional turmoil, or make signing up futile.

Potential members and patients did not sign up because they were lied to by their female spouses about some important aspect of cryonics.

Why are Women Disproportionately Hostile to Cryonics?

The most immediate and straightforward reasons posited for the hostility of women to cryonics are financial. When the partner with cryonics arrangements dies, life insurance and inheritance funds will go to the cryonics organization instead of to the partner or their children. Some nasty battles have been fought over the inheritance of cryonics patients, including attempts of family members to delay informing the cryonics organization that the member had died, if an attempt was made at alll(5). On average, women live longer than men and can have a financial interest in their husbands forgoing cryonics arrangements. Many women also cite the social injustice of cryonics and profess to feel guilt and shame that their families money is being spent on a trivial, useless, and above all, selfish action when so many people who could be saved are dying of poverty and hunger now.

A more speculative reason is that cryonics can be seen to compete with having children or family life altogether. This argument posits that if death can be overcome by technological means, surrogate immortality in the form of reproducing genes becomes redundant. This argument could even explain why many cryonicists are single men (aside from the common sense observation that few women want to date the archetypical cryonics nerd).

Another reason, articulated by several religious female spouses of male cryonicists, is separation in the afterlife. This presumes not only that cryonics works, but that it results not merely in practical immortality, but in actual immortality; a state where death never occurs and the spouse survives an infinitely long time. This position also excludes the belief common to all sects of Christianity and Islam that temporal existence, even for the living, will end with the Second Coming of Jesus Christ or an imposed end to the Universe and time of judgment by Allah. Another, perhaps more credible, but unarguably more selfish, interpretation of this position is what one of us (Darwin) has termed post reanimation jealousy. When women with strong religious convictions who give separation in the afterlife as the reason they object to their husbands cryopreservation are closely questioned, it emerges that this is not, in fact, their primary concern. The concern that emerges from such discussion is that if cryonics is successful for the husband, he will not only resume living, he may well do so for a vast period of time during which he can reasonably be expected to form romantic attachments to other women, engage in purely sexual relationships or have sexual encounters with other women, or even marry another woman (or women), father children with them and start a new family. This prospect evokes obvious insecurity, jealousy and a nearly universal expression on the part of the wives that such a situation is unfair, wrong and unnatural. Interestingly, a few women who are neither religious nor believers in a metaphysical afterlife have voiced the same concerns. The message here may be If Ive got to die then youve got to die too! As La Rochefoucauld famously said, with a different meaning in mind, Jealousy is always born with love, but does not always die with it.

Getting More Specific

While these arguments may plausibly address the hostility so many women feel toward their husbands cryopreservation arrangements, they do not address the much more common and more immediate negative reaction women typically display to even the prospect of their spouse or boyfriend becoming involved in cryonics. In such instances it could, of course, be argued that in reality these women are in fact objecting to the act of cryopreservation itself, since that is the logical outcome of their husbands involvement. The problem with this objection is that it fails to consider the reasons women often voice as being material to their hostility to cryonics. A shortlist of these objections is as follows:

o Fear of social ostracism: Involvement with cryonics is not commonplace in any society on the planet and any unusual, atypical or nonconformist behaviour carries with it the risk of reduction in social status, gossip, doubts about good judgment and rationality, and in the worst case, ridicule and ostracism.

o Embarrassment and inadequacy: Even if there is no discernible negative social impact, the fact that her husband is involved with cryonics, or worse still, signed up for neuro-cryopreservation, is frequently perceived as a source of profound embarrassment. Many women are uncomfortable being singled out or made the center of attention because of nonconformist behaviour on the part of any member of their family whose behaviour they perceive they may be held accountable for. A closely related concern is that they will be put in the position of having to both explain and justify their husbands unconventional choice. Such explanations and justifications are often correctly perceived to require considerable understanding of the premises, underlying scientific arguments, and most troubling, a detailed explication of the biomedical procedures used to induce cryopreservation as well as the physical and financial aspects of long term cryogenic care. This leaves out the even more daunting mastery of the scientific, technological, social and philosophical arguments that address the issue of reanimation and reintegration of cryonics patients into society. Also unaddressed are the thorny issues of the theological and ethical issues cryonics raises.

o Resource drain: Women understand that their husbands and boyfriends have interests, hobbies and avocations which are not a part of their romantic or even day-to-day relationship. Preoccupation with sports, automobiles, fishing, boating, golfing, or costly or dangerous pursuits, such as scuba diving or sky diving are frequently sources of friction in marriages. These activities inevitably result in a drain of both time and money spent with the wife and children time and money that could clearly be spent improving the quality and quantity of martial life, as well as providing assets for education of the children and additional savings to serve as a reserve in hard economic times, or times of family crisis.

o The prospect of homosocial or ideologically-driven alienation: Many, if not most, women object to exclusively or strongly homosocial activity on the part of their spouses. The social structure in most of the world today is predominately homosocial, wherein heterosexual men engage heavily or even almost exclusively in social (not sexual) interaction with other men. In these societies women are excluded from discussion of ideas, politics, business, current events, and usually religion. Until the mid-20th Century the social fabric of the U.S. and Europe was predominately homosocial with women retiring to a separate area of the home while men discussed politics, philosophy, the arts and sciences, and other non-domestic issues. Heterosexual men, past and present, also like to engage in exclusively homosocial activities ranging from the informal boys night out to more structured ventures such as camping, hunting and participation in male-only fraternal organizations. That these activities can and do lead some men to spend large fractions of their non-working time involved in such activities is a well known and wholly justified source of concern to women. After even glancing contact with cryonics, women quickly perceive that cryonics, and particularly activist cryonics, is populated almost exclusively by men and therefore represents a homosocial threat. It should also be noted that after men marry it is typical that much or even all of their socializing with their single male friends stops.

An even more anxiety provoking prospect is that of ideological alienation of the husband from his wife and family. Regardless of whether or not cryonics is perceived as a cult, it is justifiably understood to embrace a world view and a value system that is radically different from both the social norm and from the philosophical and ideological perspective of the wife or that which the husband and wife shared before cryonics was introduced into the equation. Wives often express anxiety and concern that their husbands may change drastically in both beliefs and behavior as a result of involvement with cryonics and that this might result in alienation within the marriage or even divorce.

o Religious and childrearing concerns: Most people of faith, regardless of gender, will have questions over the compatibility of cryonics and religion, at least when they first seriously contemplate the idea. To the deeply religious, absent a clear statement from the understood authority in their faith (the Pope, minister or church council, rabbi, or one of the hojjatoleslam in Islam) cryonics may be the source of lasting anxiety and uncertainty about whether it really is compatible with their faith. Even absent concerns about the religious acceptability of cryonics per se, there are often concerns about its impact on the religiosity and adherence to cultural values on the part of the children. The majority of observant Jews in both the U.S. and Israel are agnostic or atheist, but still highly value and consider critical to their survival and identity observance of Jewish cultural practices and rituals. Cryonics is often perceived as contrary to or corrosive of these values and practices.

o Other women: While cryonics is mostly a male pursuit, there are women involved and active, and many of them are single. Wives (or girlfriends) justifiably worry that another woman who shares their husbands enthusiasm for cryonics, shares his newly acquired world view and offers the prospect of a truly durable relationship one that may last for centuries or millennia may win their husbands affections. This is by no means a theoretical fear because this has happened a number of times over the years in cryonics. Perhaps the first and most publicly acknowledged instance of this was the divorce of Fred Chamberlain from his wife (and separation from his two children) and the break-up of the long-term relationship between Linda McClintock (nee Linda Chamberlain) and her long-time significant other as a result of Fred and Linda working together on a committee to organize the Third National Conference On Cryonics (sponsored the Cryonics Society of California).

The Underlying Reason?

While few would argue that there are not large, statistically demonstrable differences between men and women in terms of temperament, exploratory and risk taking behaviour as well as religiosity and intellectual and recreational pursuits, there is intense controversy as to whether these differences are due to biology, or to cultural and social factors that both limit and warp womens innate intellectual and behavioral parity with men. Regardless of whether these observed differences are rooted in nature or nurture, biology or culture, they are certainly real and they have had enormous impact on society and on the dynamic between men and women.

In his remarkable book, Human Accomplishment: The Pursuit of Excellence in the Arts and Sciences, 800 BC to 1950 (HarperCollins, New York, 2003, ISBN 0-06-019247-X) Charles Murray evaluates the origin and the creators of human artistic, scientific, technological and intellectual accomplishments over the span of what is essentially recorded history. Murray does this using the arguably objective procedure of calculating the amount of space allocated to these individuals in reference works, peer reviewed publications and other easily objectifiable measures of intellectual significance. Murray uses the well developed and widely accepted technique of historiometry, which is the historical study of human progress or individual personal characteristics, using statistics to analyze references to famous people and their discoveries in relatively neutral texts. Historiometery traces its origins to the work of Adolphe Quetelet, a 19th Century Belgian mathematician, who primarily studied the relationship between age and intellectual or artistic achievement.

Murray found that nearly all scientific progress, and all important scientific and artistic ideas, were made by white Europeans or their descendants (such as white Americans, Australians, Canadians, and New Zealanders). With few exceptions these core innovators were also male.

A number of studies have evaluated risk-taking behavior in males as contrasted with females. These studies have predominately concluded that men are not only bigger risk-takers, but that they engage in much more dangerous risk taking(7). An elegant and objective evaluation of sex-related differences in the selection of a successful strategy when facing novelty is the work of Catherine Brandner, who used a simple visuo-spatial task to investigate exploratory behavior as a specific response to novelty. Brandner found that strategies used by women and men to solve an exploratory task that may be seen as involving a trading off of risk versus reward differed markedly by gender. Brandner concludes: This study has first shown that the searching strategies used by women and men to solve an exploratory task that may be seen as involving trading off of risk and reward differed according to sex. Women adopted a local searching strategy in which the metric distance between what is already known and what is unknown was reduced. Men adopted a global strategy based on an approximately uniform distribution of choices. These findings appear to be compatible with a female frame of mind expressing careful consideration of all circumstances and possible consequences before making a decision.

Unquestionably, cryonics can be classified as risk-taking activity and exploratory behavior (one-way time travel to the future!) and it is also dependent upon a global approach to problem solving as opposed to the more meticulous and incremental approach to problem solving favored by women. Cryonics also demands paradigm changing innovative thinking that is closely allied with, if not identical to, the kinds of scientific, artistic and cultural thought that Murray has demonstrated are almost exclusively the province of males, and white males at that (which also raises the issue of why so few people of color are involved in cryonics). Perhaps it is these fundamental differences between men and women that determine not only male preference for, and general lack of hostility to, cryonics (at least as regards spouses and other immediate family members choices), but also the existence of a subgroup of women who are virulently opposed to cryonics, or more accurately, to the involvement of their husbands in cryonics.

Conclusion

Although the hostility of some women to their partners cryonics arrangements and activism is disturbing, the phenomenon is real. One high profile cryonicist once said: You can get another wife, but you cant get another life. Such words of wisdom need to be heeded, but it is understandable that some cryonicists need to make a trade-off between cryonics and other values. Hopefully, the forgoing analysis will offer some concrete areas of potential conflict, perceived or real, that can be addressed by both emotional reassurance and reason. Identifying the problems is certainly a necessary first step to resolving them.

Endnotes

1. Brenda Peters, a long-time female cryonics activist, Alcor Board member and Founding President of CryoCare was married to a Hollywood screenwriter and producer and has stated, while by no means the sole reason for dissolution of her marriage, cryonics played an important role in the breakup. Former Alcor Treasurer and stalwart cryonicist Sherry Cosgrove faced a similar ultimatum in 1987 and chose to cease active involvement in cryonics and revoke her cryopreservation arrangements.

2. Interview of Curtis Henderson by Mike Darwin, 22 November, 2007, Ash Fork, AZ.

3. Alcor patient A-1036 suffered ~10 minutes of ischemic injury without cardiopulmonary support due to interference from his sister and female business partner. A-1049 suffered ~30 minutes of ischemic injury due to interference from his mother and sister.

4. Alcor patient A-1242 was removed from cryopreservation under court order as a result of litigation brought against Alcor and the patients husband by the patients sister, who objected to cryopreservation. Alcor patient A-2127 died while in the sign up process due to hostile female relatives. Alcor patient A-1099 suffered prolonged ischemia, embalming and straight freezing and was almost cremated due to the non-compliance of his sisters with his cryonics arrangements.

5. Alcor patient A-1242 was removed from cryopreservation under court order as a result of litigation brought against Alcor and the patients husband by the patients sister, who objected to cryopreservation. Alcor patient A-2127 died while in the sign up process due to hostile female relatives. Alcor patient A-1099 suffered prolonged ischemia, embalming and straight freezing and was almost cremated due to the non-compliance of his sisters with his cryonics arrangements.

6. http://www.lifepact.com/history.htm

7. Pyszczynski, Tom L. (Feb. 2002) Gender differences in the willingness to engage in risky behavior: A terror management perspective. Death Studies, 26, 117-142.

Risk taking influenced by sense of control, claims US psychology professor. (Nov. 2001). http://www.psycport.com retrieved on Oct. 10, 2002.

Wagner, Mervyn K. (Jan./Feb. 2001). Behavioral characteristics related to substance abuse and risk-taking, sensation- seeking, anxiety sensitivity and self-reinforcement. Addictive Behaviors, 26, 115-120.

8. Brandnery, C Strategy selection during exploratory behavior: sex differences Judgment and Decision Making. Vol. 2, No. 5, October 2007, pp. 326332.

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Scientists have used a popular gene editing tool called CRISPR to snip out a tiny piece of DNA from one particular gene in a white button mushroom. The resulting mushroom doesn't brown when cut. Adam Fagen/Flickr hide caption

Scientists have used a popular gene editing tool called CRISPR to snip out a tiny piece of DNA from one particular gene in a white button mushroom. The resulting mushroom doesn't brown when cut.

There's a genetic technology that scientists are eager to apply to food, touting its possibilities for things like mushrooms that don't brown and pigs that are resistant to deadly diseases.

And food industry groups, still reeling from widespread protests against genetically engineered corn and soybeans (aka GMOs) that have made it difficult to get genetically engineered food to grocery store shelves, are looking to influence public opinion.

The technology is called Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR. It's a technique that Alison Van Eenennaam, an animal genetics professor at University of California, Davis, says can de-activate a gene. Or, as she puts it: "It's editing. It's like going into a Word document and basically replacing one letter, maybe that instead of 'wind,' you want it to say 'wine,' " she says.

Skeptics, like Dana Perls with the environmental group Friends of the Earth, say food companies are trying to distance themselves from terms like GMO and genetic engineering that have caused them trouble with consumers.

"These new gene editing technologies like CRISPR are genetic engineering. And if this is genetic engineering, then call it that," says Perls. She says these producers are just trying to pull the wool over consumers' eyes with a strong public relations push.

Dozens of crops and livestock developed with CRISPR technology are years from the market, though the U.S. Department of Agriculture already said it won't regulate CRISPR-developed products like other genetically engineered food, since no foreign genetic material is introduced in the process. The Food and Drug Administration will decide which new products are safe.

To get ahead of any criticism, a group of heavyweights in the food industry have joined forces to form the Coalition for Responsible Gene Editing in Agriculture, which is funded by members like the U.S. Pork Board, Monsanto, Syngenta and Bayer.

The board's CEO, Bill Even, says the food industry missed a chance to do this when the earlier wave of genetically engineered food made it to the market.

"There was never any conversation with consumers around what is this and what did it mean," he says. "Fast forward now today, there's a lot of debate around GMOs and food. The public rightly [is] ... interested in knowing what's in their food."

People don't often trust big companies, says Charlie Arnot, who leads the coalition and is the CEO of the Center for Food Integrity. But when it comes to CRISPR, there are three key strategies Arnot says will help get consumers on board.

First: CRISPR is not a secret.

"Those in technology have to be more transparent and be much more engaged in a public conversation and dialogue, in order to answer those questions, address the skepticism and ultimately result in earning consumer trust in what they're doing in gene editing," he says.

Second, the coalition wants to show that it shares the same values that shoppers do. So, its members are sponsoring and attending events like CRISPRcon to engage in public discussions about the technology and its potential animal welfare, societal and environmental benefits.

"If people trust you, science doesn't matter. If people don't trust you, science doesn't matter," Arnot says. "It only matters after you cross that trust threshold. So you really have to engage in that values-based dialogue to build trust, and then you're given the permission to introduce the science."

And that's the third strategy: These companies want consumers to know that CRISPR isn't like other forms of genetic engineering. CRISPR changes the way genes are expressed; it doesn't necessarily add genetic material from another species, although it can be used that way.

"That's going to be the path that will ultimately lead to greater trust," Arnot says. "If we shortcut that path, we run the risk of potentially having this significantly beneficial technology not be accepted."

But persuading consumers to buy into CRISPR will be an uphill battle for Arnot and other industry groups. Food and environmental advocacy groups already are asking questions about CRISPR, as well as raising concerns over tracing genetically edited food in the system and the potential lack of regulatory oversight.

This story comes to us from Harvest Public Media, a reporting collaboration that focuses on agriculture and food production. Kristofor Husted is based at member station KBIA in Columbia, Mo.

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Scientists have used a new gene-editing technique to create pigs that can keep their bodies warmer, burning more fat to produce leaner meat. Infrared pictures of 6-month-old pigs taken at zero, two, and four hours after cold exposure show that the pigs' thermoregulation was improved after insertion of the new gene. The modified pigs are on the right side of the images. Zheng et al. / PNAS hide caption

Scientists have used a new gene-editing technique to create pigs that can keep their bodies warmer, burning more fat to produce leaner meat. Infrared pictures of 6-month-old pigs taken at zero, two, and four hours after cold exposure show that the pigs' thermoregulation was improved after insertion of the new gene. The modified pigs are on the right side of the images.

Here's something that may sound like a contradiction in terms: low-fat pigs.

But that's exactly what Chinese scientists have created using new genetic engineering techniques.

In a paper published Monday in the Proceedings of the National Academy of Sciences, the scientists report that they have created 12 healthy pigs with about 24 percent less body fat than normal pigs.

The scientists created low-fat pigs in the hopes of providing pig farmers with animals that would be less expensive to raise and would suffer less in cold weather.

"This is a big issue for the pig industry," says Jianguo Zhao of the Institute of Zoology at the Chinese Academy of Sciences in Beijing, who led the research. "It's pretty exciting."

The genetically modified low-fat piglets Jianguo Zhao hide caption

The animals have less body fat because they have a gene that allows them to regulate their body temperatures better by burning fat. That could save farmers millions of dollars in heating and feeding costs, as well as prevent millions of piglets from suffering and dying in cold weather.

"They could maintain their body temperature much better, which means that they could survive better in the cold weather," Zhao said in an interview.

Other researchers call the advance significant.

"This is a paper that is technologically quite important," says R. Michael Roberts, a professor in the department of animal sciences at the University of Missouri, who edited the paper for the scientific journal. "It demonstrates a way that you can improve the welfare of animals at the same as also improving the product from those animals the meat."

But Roberts doubts the Food and Drug Administration would approve a genetically modified pig for sale in the United States. He's also skeptical that Americans would eat GMO pig meat.

"I very much doubt that this particular pig will ever be imported into the USA one thing and secondly, whether it would ever be allowed to enter the food chain," he says.

The FDA has approved a genetically modified salmon, but the approval took decades and has been met with intense opposition from environmental and food-safety groups.

Others say they hope genetically modified livestock will eventually become more acceptable to regulators and the public.

"The population of our planet is predicted to reach about 10 billion by 2050, and we need to use modern genetic approaches to help us increase the food supply to feed that growing population," says Chris Davies, an associate professor in the school of veterinary medicine at Utah State University in Logan, Utah.

Zhao says he doubts the genetic modification would affect the taste of meat from the pigs.

"Since the pig breed we used in this study is famous for the meat quality, we assumed that the genetic modifications will not affect the taste of the meat," he wrote in an email.

The Chinese scientists created the animals using a new gene-editing technique known as CRISPR-Cas9. It enables scientists to make changes in DNA much more easily and precisely than ever before.

Pigs lack a gene, called UCP1, which most other mammals have. The gene helps animals regulate their body temperatures in cold temperatures. The scientists edited a mouse version of the gene into pig cells. They then used those cells to create more than 2,553 cloned pig embryos.

Next, scientists implanted the genetically modified cloned pig embryos into 13 female pigs. Three of the female surrogate mother pigs became pregnant, producing 12 male piglets, the researchers report.

Tests on the piglets showed they were much better at regulating their body temperatures than normal pigs. They also had about 24 percent less fat on their bodies, the researchers report.

"People like to eat the pork with less fat but higher lean meat," Zhao says.

The animals were slaughtered when they were six months old so scientists could analyze their bodies. They seemed perfectly healthy and normal, Zhao says. At least one male even mated, producing healthy offspring, he says.

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T

he acronyms might not be quite as catchy as CRISPR since, really, what is? but what new genetic tools dubbed REPAIR and ABE lack in whimsy they promise to make up in utility. These advances announced Wednesday solve two of the problems hobbling CRISPR, the revolutionary genome-editing technique: that its idea of editing is often like 1,000 monkeys editing a Word document, and that making permanent changes to DNA might not be the best approach.

Together, the discoveries, described in separate studies, show that five years after scientists demonstratedthat CRISPR can edit DNA, bioengineers are still racing to develop the most efficient, precise, versatile and therefore lucrative genome-editing tools possible.

One reason these are so exciting is, they show the CRISPR toolbox is still growing, said chemical engineer Gene Yeo of the University of California, San Diego. There are going to be a lot more, and its not going to stop anytime soon. His lab has been working on one of the CRISPR advances but was not involved in either of the two new studies its personally frustrating to get beaten, he added.

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One discovery, led by biochemist David Liu of Harvard University, extends his 2016 inventionof a way to change a single DNA letter, or base, on the 3-billion-letter-long human genome. Classic CRISPR cuts DNA with a molecular scissors and leaves the cell to repair the breach willy nilly, introducing the problem of 1,000 monkeys editing away. In contrast, Liusbase editor replaces the molecular scissors with something like a pencil wielded by an expert forger: It is an enzyme that literally rearranges atoms cleanly and without collateral damage that the cell needs to fix.

As in classic CRISPR, this version finds its way to a target on the genome via a molecule that acts like a bloodhound. Attached to the bloodhound is the atom-rearranger, which in Lius 2016 version turned the DNA letterG into A. Thousands of genetic diseases arise because a gene has a G where it should have an A,so the edit might one day treat or prevent them.

But other inherited disorders need different alphabetical magic. Thats what Liu, postdoctoral fellows Nicole Gaudelli and Alexis Komor, and their colleagues report in a paper in Nature: Their new ABE (adenine base editor) can turn A into G.Attached to CRISPRs bloodhound molecule, ABE works at virtually any target site in genomic DNA, Liu said.

In tests so far, it changed DNA in more of the lab-grown human cells thatit was slipped into than standard CRISPR (for all its fame, CRISPR often bungles the job). ABE also seems to make fewer off-target edits: In one test, it mistakenly hit four of the 12 off-target sites, compared to CRISPRs nine, and made that mistake in 1.3 percent of cases compared to 14 percent for CRISPR, Liu said.

About half of the 32,000 known disease-causing, single-letter mutations have one of the misspellings that ABE can fix, Liu said. They include sickle cell, Tay-Sachs, and cystic fibrosis, raising hopes that ABE could be used to treat these diseases, or (in early embryos) prevent them.In tests of cells growing in lab dishes, ABE reversed the mutation that causes hereditary hemochromatosis in about 30 percent of the cells, and changed another gene into a form that prevents sickle cell disease even in people who have its disease-causing mutation.

As with all forms of CRISPR, before ABE helps any patients, scientists will have to test whether its safe and effective. But having the molecular machine is a good start, said Liu, a co-founder of the CRISPR company Editas Medicine. He and colleagues have filed for patents on ABE.

Harvard biologist George Church, who tied for first in the race to make CRISPR work in human cells, called base editing especially interesting. Changing a single DNA letter, he said, means fewer worries about the editing enzyme [in classic CRISPR] later going rogue or silent. He also expects that crops with a single base change will not be designated as transgenic, reducing regulatory barriers to commercialization.

In a separate study, CRISPR pioneer Feng Zhang of the Broad Institute and his colleagues discovered a new version of CRISPR that can edit RNA, DNAs friskier cousin. While DNA mostly sits sedately in cells and issues orders to make proteins that keep life living, RNA zips around the cell carrying out those orders, and then disappears. That makes RNA a tantalizing target: By editing the errant orders (RNA) rather than their issuer (DNA), scientists might be able to make temporary, reversible genetic edits, rather than CRISPRs permanent ones.

Editing DNA is hard to reverse, but once you stop providing the RNA-editing system, the changes will disappear over time, said Zhang, also a co-founder of Editas. That might make it possible to treat conditions where you dont need a permanent edit, such as when the immune system is in overdrive and causing inflammation.

To create what Zhang and his colleagues call REPAIR (RNA editing for programmable A to I [G] replacement), they fused an enzyme that binds to RNA with one that changes the RNA letter A (adenosine) to inosine, a molecule similar tothe RNA letter G (guanosine), they report in Science.Other labs, including that of CRISPR developer Jennifer Doudna of the University of California, Berkeley, have also developed RNA editors, including one using the same Cas13 enzyme. But REPAIRs creators say theirs is more efficient and less error-prone.

In tests on human cells growing in the lab, REPAIR corrected misspellings in theRNA that was made by disease-causing DNA in this case, Fanconi anemia, an inherited and devastating bone marrow disease, or nephrogenic diabetes insipidus, a serious inborn kidney disease. Although the DNA still had its disease-causing mutations, 23 percent and 35 percent, respectively, of the RNA made by those defective genes was REPAIRed. Those levels might be high enough to treat the diseases. Some 5,800 inherited diseases are the result of the G-to-A glitch that REPAIR can fix, including epilepsy and Duchenne muscular dystrophy.

Both REPAIR and ABE might venture where CRISPR stumbles: in mature cells, like neurons, that dont divide. In unpublished research, Liu said, he and his team have shown that ABE can edit genes in neurons, raising the possibility of treating devastating neurological diseases with ABE.

The furious race to improve CRISPR, via ABE or REPAIR or whatever comes next, Church said, are potent reminders of how far CRISPR is from precise genome-editing in humans.

Senior Writer, Science and Discovery

Sharon covers science and discovery.

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The CRISPR Pill made headlines with its implications in the fight against Superbugs.

But CRISPR technology originated from research into gene splicing and genetic editing capabilities. Since DNA is the fundamental building block of existence, what CRISPR claims it can do is bold and a little terrifying.

What are the real-world applications and implications of this biotech?

The above image comes from a YouTube video produced by the McGovern Institute for Brain Research at MIT from 2014. You can see that it involves gene splicing. One of the faculty members, Feng Zhang, led a team of researchers at MIT on the project, but many groups have looked into CRISPR-Cas9 biotech.

As early as 1993, researcher Francisco Mojica of the University of Alicante in Spain tinkered with CRISPR. Fun fact: the CRISPR DNA sequenceandCas-9 enzyme are a naturally occurring defense mechanism in various bacteriamost notably the kind that causes strep throat.

Yeswe derived gene editing biotech from that pestering, cold weather (but also any time weather because its bacteria based) illness.

But dont worry: the CRISPR-Cas9 strand operates similarly to bacteriophages.

It repeats a series of the same DNA sequences with unique sequences peppered in. These clusters became known as clustered regularly interspaced short palindromic repeats.

Though Ruud Jansen first used the term CRISPR in 2002, Mojica adopted the initialization throughout his research in discovering that CRISPR is basically an adaptive immune system.

This led others to tinker with the bacteria-based defense mechanism, as well. In 2005, Alexander Bolotin of the French National Institute for Agricultural Research discovered the unusual Cas-9 protein displaying nuclease activity. He specifically noted it in the Streptococcus thermophilus bacteria as opposed to other bacteria. Bolotin also discovered a PAM(protospacer adjacent motif) which allows for target recognition.

From there, a plethora of scientists and researchers began to experiment with CRISPR and Cas-9 DNA sequences.

Knowing how something came to be is all fine and good, but exactly how does CRISPR work? Simple: it acts similarly to how viruses do when they attack organisms human or otherwise. Copies of the attacking virus DNA are made with temporary RNA. Then, these copies attach themselves to the attacked organism, forcing replication. This is how viruses infect things and its also how bacteriophages work, too.

Since researchers can now harness the power of CRISPR-Cas9 (bacterias own natural defense system against infection) many believe they can utilize this against antibiotic resistant strains of bacteria.

So, DNA has four amino-acid bases: adenine (A), thymine (T), guanine (G), and cytosine (C).

DNA will target any sequence acting a bit off to forego any potential damage. However, the CRISPR-Cas9 system operates differently since it can read 20 bases in any sequence. This elf-eyes-esque sight allows for better tailoring to a specific gene. There is even an online tool you can use to design a target sequence and how the RNA should interact with it.

While the implications of this are monstrous, the real world applications do meet with a few stumbling blocks. One such block: the fact that the enzymes sometimes cut at the wrong place. Clearly, when it comes to gene editing, you want to be able to hit your mark every time.

While the research into gene editing biotech has come a very long way, genetically engineered babies are still a bit further down the roador are they? Researchers in Portland, Oregon successfully edited a human embryo in 2017.

However, this falls under the category of germlinecells or reproductive cells. While the editing of somatic (or non-reproductive) cells is generally not controversial, editing reproductive cells raises several ethical dilemmas.

Despite this moral hang-up, use of CRISPR-Cas9 gene editing tech is already underwayeven in robotics. Transcriptics robotic lab added this biotech to its list of services in 2015 in hopes to save time and money in the gene editing process. China instigated human trials in 2016, and we dont even need to mention the implications regarding infectious diseases like Malaria.

We may have far to go with genetic editing and the fight against superbugs and viruses. But, we have taken very necessary and BIG first steps.

With how far genetics has come in the last 30 years, we have to wonder how advancements in robotics and biotech will propel things even further.

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Provided by The Verge

The powerful gene-editing tool CRISPR has been making headlines for its ability to edit DNA, which could one day transform how we fight cancer and other life-threatening diseases. Now, scientists have created a new version of CRISPR that can target and edit a different genetic building block: RNA.

The new tool, described in a study published today in Science, offers several advantages: its edits, for instance, arent permanent, which makes gene editing much safer. Researchers showed that the new system, called REPAIR, can work relatively efficiently in human cells. In the future, it could be used to treat diseases, as well as better understand the role that RNA plays in causing those diseases.

Its another tool in the toolbox.

Its another tool in the toolbox that we didnt have access to before, says Mitchell O'Connell, assistant professor in the Department of Biochemistry and Biophysics at the University of Rochester, who was not involved in the research. Its like developing new technology that makes you see things that you couldn't see before, or tweak things that you couldn't tweak.

The gene-editing tool CRISPR is based on a defense mechanism bacteria use to ward off viruses by cutting off bits of their DNA and pasting them elsewhere. Scientists have engineered that mechanism to tweak DNA, creating unusually muscular beagles, for instance, and mosquitoes that dont transmit malaria. But there are different types of CRISPR, with different types of molecular scissors. The gene-editing tool thats been making lots of headlines is called CRISPR-Cas9. The CRISPR used in todays study is called CRISPR-Cas13.

Instead of snipping DNA, this type of CRISPR targets another of the major biological molecules found in all forms of life, RNA. Most of the time, RNA is used inside the body to help DNA build proteins. And proteins play an important role in causing diseases. There are some advantages to editing RNA instead of DNA, says study co-author David Cox, a PhD student in the Zhang Lab at the Broad Institute of MIT and Harvard, which has been doing pioneering work on CRISPR. RNA is constantly being made and recycled inside cells, so an RNA edit is not permanent. (The edits could still be effective, though: the CRISPR system could be kept in cells for, say, months, allowing the scissors to keep editing RNA as it forms.) That makes the whole process safer. If you edit RNA and make a mistake, for instance, the faulty RNA will be degraded likely within 24 hours. Instead, if you edit DNA and make a mistake, that mistake is irreversible and could possible lead to cancer. Certain changes to DNA could also be passed on to future generations, while changes to RNA generally arent passed on.

there are still big risks involved.

Gene editing is very exciting, but there are still big risks involved, O'Connell tells The Verge. Targeting RNA rather than DNA is a safer strategy, particularly for things where you might not want to make permanent change.

To create the new editing tool, called REPAIR, the researchers combined CRISPR-Cas13 with a protein called ADAR. It works this way: the Cas13 enzyme is programmed to target a specific RNA sequence that might correspond to a disease mutation; the ADAR protein then makes the edit. In the study, the researchers showed that the system can edit specific RNA bases with 20 to 40 percent efficiency and up to 90 percent in some instances, says Cox. And the system made few mistakes: even though gene-editing tools are very precise, sometimes they snip pieces of genetic code they werent programmed to cut. These off-target cuts can be dangerous, and scientists want to make sure there are as few of them as possible.

A first version of REPAIR caused nearly 20,000 off-target cuts, says study co-author Omar Abudayyeh, also a PhD student in the Zhang Lab. That was a pretty disappointing moment, he tells The Verge. But then, the team tweaked the system in a way that reduced the number of off-target cuts to 10 to 20 per target site, making it much more precise and safe.

O'Connell says he was surprised by how well the system works. RNA has been targeted before in an effort to make drugs to treat disease, O'Connell says. But this CRISPR system makes the whole editing process much easier. In the future, this editing tool could be used to treat life-threatening diseases like hemophilia, as well as a heart condition called hypertrophic cardiomyopathy, which can lead to sudden death, Cox tells The Verge. Before that happens, the system needs to be optimized, and made much more precise. Researchers also need to show that it works in mice, other animals, and eventually in people. Its a long road to translate this into any sort of therapy, says study co-author Jonathan Gootenberg, another PhD student in the Zhang Lab.

You feel so empowered where youre in the lab.

Together with CRISPR-Cas9, this system really has the potential to revolutionize how we treat diseases. And thats the motivation that keeps Gootenberg, Cox, and Abudayyeh working hard in their lab. Abudayyeh says that when he was in med school, he met a woman with terminal lung cancer, who had maybe a few more months to live. You feel pretty hopeless in that situation because theres nothing you can do even as a doctor, he says. But thats also what inspired him to get into biotechnology.

You feel so empowered where youre in the lab, just thinking about new ways to make new technologies with the potential to hopefully actually help patients like that, Abudayyeh says. Its really exciting.

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A stem cell or bone marrow transplant replaces damaged blood cells with healthy ones. It can be used to treat conditions affecting the blood cells, such as leukaemia and lymphoma.

Stem cells arespecial cells produced bybone marrow (aspongytissue found in the centre of some bones) that can turn into different types of blood cells.

The three maintypes of blood cellthey can become are:

A stem cell transplant involves destroying any unhealthy blood cells and replacing them with stem cells removed from the blood or bone marrow.

Stem cell transplants are used to treat conditions in which the bone marrow is damaged and is no longer able to produce healthy blood cells.

Transplants can also be carried out to replace blood cells that are damaged or destroyed as a result of intensive cancer treatment.

Conditions that stem cell transplants can be used to treat include:

A stem cell transplant will usually only be carried out if other treatments haven't helped, the potential benefits of a transplant outweigh the risks and you're in relatively good health, despite your underlying condition.

A stem cell transplant can involve taking healthy stem cells from the blood or bone marrow of one person ideally a close family member with the same or similar tissue type (see below) and transferring them to another person. This is called an allogeneic transplant.

It's also possible to remove stem cells from your own body and transplant them later, after any damaged or diseased cells have been removed. This is called an autologous transplant.

Astem celltransplant has five main stages. These are:

Having a stem cell transplant can be an intensive and challenging experience. You'll usually need to stay in hospital fora month or more until the transplant starts to take effect and itcan takea year or two to fully recover.

Read more about what happens during a stem cell transplant.

Stem celltransplants arecomplicated procedures with significant risks. It's important that you're aware of both the risks and possible benefits before treatment begins.

Possible problems that can occur during or after the transplant process include:

Read more about the risks of having a stem cell transplant.

Ifit isn't possible to use your own stem cells for the transplant (see above), stem cells will need to come from a donor.

To improve the chances ofthetransplant being successful, donated stem cells need tocarry a special genetic marker known as a human leukocyte antigen (HLA) that'sidentical or very similar to that of the person receiving the transplant.

The best chance of getting a match is from a brother or sister, or sometimes another close family member. If there are no matches in your close family,a search of theBritish Bone Marrow Registry will be carried out.

Most peoplewill eventually find a donor in the registry,although a small number of people may find it very hard or impossibleto find a suitable match.

The NHS Blood and Transplant website has more information about stem cell and bone marrow donation.

Page last reviewed: 08/10/2015

Next review due: 01/10/2018

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Photo: LOREN ELLIOTT, Special To The Chronicle

A heat map illustrates how effectively mutated cells blocked HIV, in a UCSF lab.

A heat map illustrates how effectively mutated cells blocked HIV, in a UCSF lab.

How CRISPR gene-editing tech can fight HIV

Researchers at UCSF have received a three-year, $1.6 million grant to advance their work using novel gene-editing technology to make human blood cells less susceptible to HIV infection.

The grant, from biopharmaceutical giant Gilead Sciences, a global leader in sales of HIV treatments, will fund a team of scientists working to modify the DNA of a type of white blood cell to make them immune to HIV infection.

The cells, called T cells, have long been a focus of researchers seeking to improve HIV treatments. T cells help the immune system fight many diseases, including some cancers and flu viruses. They play a unique role in HIV because the virus targets and destroys T cells, and HIV-positive patients whose T cells become too depleted by the virus will progress to AIDS.

Using a gene-editing technique known as CRISPR, the UCSF researchers have already tested dozens of genes believed to play a role in how HIV spreads within the body. They do this by collecting blood samples from HIV-negative patients, altering the DNA of those cells, and then introducing the HIV virus to the modified cells in test tubes. Within two weeks, they can see whether the change to the gene has eliminated the cells ability to become infected with HIV.

CRISPR can be used to modify the DNA of plants, animals and other living organisms. It is considered a groundbreaking method because it is simpler and cheaper than other gene-editing techniques.

This is connecting CRISPR to HIV and opening up whole new avenues of research in understanding the interplay between human genetics and HIV, said Alex Marson, an assistant professor of microbiology and immunology at UCSF who leads the lab that received the Gilead grant.

The grant, announced this week, will allow Marsons lab to pursue an ambitious goal of uncovering why HIV remains dormant in some cells, only to awaken unpredictably, sometimes years later. Known as HIV latency, this characteristic of the virus is why HIV-positive patients must take antiretroviral drugs which are only effective in attacking the awake HIV for life.

The tricky thing about HIV, and one reason its so hard to cure, is that it can hide in the DNA of the human cells, said Joe Hiatt, a doctoral student of medicine and philosophy in Marsons lab and a leader in the research initiative. It becomes DNA and integrates into your DNA.

The problem has perplexed researchers for years. But Marson and Hiatt see potential for using CRISPR to discover which genes control HIV latency. They hope to use the gene-editing tool to create latent HIV cells in test tubes, and then modify the DNA in those cells to see which edits may coax the HIV out of hiding and make it susceptible to drugs. This will be the most challenging and complicated part of the research. If done successfully, it could lead to the development of drugs that target latent HIV and perhaps cure HIV permanently.

CRISPR technology is potentially revolutionary because HIV is a type of virus that will sneak its own genetic code into the genetic code of the human cell, said Ross Wilson, a scientist at UC Berkeleys Innovative Genomics Institute who is not involved in the grant. Its like hiding a book in a stack at the library, and the book has instructions to build a nasty bomb. To get rid of that information, you need to get it back out of the library. Weve never had the technology to do that inside the living cell until CRISPR came along. Its the first efficient way to do that inside living cells.

It is the first research initiative that Foster Citys Gilead, through its philanthropic program, has funded that involves using CRISPR as a tool in HIV cure-related research. While $1.6 million is not a huge amount, it comes with fewer restrictions than many government grants. The grant will fund a team of five researchers for three years.

It is one of five grants totaling $7.5 million, announced this week, that Gilead has awarded research institutions for HIV and AIDS-related initiatives. The others are to the University of Massachusetts Medical School; Dana-Farber Cancer Institute; Institute of Human Genetics, French National Center for Scientific Research and University of Montpellier; and Frederick National Laboratory for Cancer Research, AIDS and Cancer Virus Program.

A Gilead spokesman said that if the UCSF researchers discover how latent HIV can be targeted by drugs, the company will not necessarily have rights to licensing agreements or other commercial benefits. The grant is from the companys philanthropy program and is meant to support HIV research independent of Gileads business interests, he said.

Catherine Ho is a San Francisco Chronicle staff writer. Email: cho@sfchronicle.com Twitter: @Cat_Ho

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Photos from Eadweard Muybridges study of a galloping horse have been recorded in bacterial DNA

Eadweard Muybridge/The LIFE Picture Collection/Gett

By Douglas Heaven

Life is an open book and were writing in it. A team at Harvard University has used the CRISPR genome-editing tool to encode video into live bacteria demonstrating for the first time that we can turn microbes into librarians that can pass records on to their descendants and perhaps to ours.

The technique could even let us create populations of cells that keep their own event logs, making records as biological processes like disease or brain development happen.

DNA is one of the best media for storing data we know of. Researchers have already crammed large amounts of information from books to digital images into tiny amounts of biological material. In theory, a gram of single-stranded DNA can encode 455 exabytes, or roughly 100 billion DVDs.

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Most previous DNA storage work has used artificial DNA: digital information is translated into a DNA sequence that is then synthesized.

However, using CRISPR lets you cut and paste the digital information directly into the DNA of a live organism, in this case a large population of E. coli.

Bacteria use the CRISPR/Cas9 system to record information in their DNA about viruses they encounter. And this machinery has been co-opted by researchers to enable us to precisely edit genomes.

In bacteria, each new entry gets stored upstream of the last one, which makes it possible to read off a history of events in the order they happened. Previous groups have created lifelogging cells by using CRISPR/Cas9 to mark the genome when a particular event occurs. But these marks just provide a tally of how many times something happens.

Seth Shipman at Harvard University and his colleagues have now used a version of CRISPR with a different enzyme, called CRISPR/Cas1-Cas2. This let them add a message to the genome rather than simply cut a notch.

The message was a recorded image of a human hand and five images showing a galloping horse, taken from Eadweard Muybridges 1878 photographic study of the animals motion, which has since been animated.

Seth Shipman

To get the DNA sequences encoding this data inside the cells, the team applied an electrical current that opened channels in the cells walls and the DNA flowed in. Once inside, CRISPR got to work.

To read the data back again, the team sequenced the DNA of more than 600,000 cells. The large number is necessary because most cells will not have edited their genome entirely accurately. Every cell isnt going to acquire every piece of information we throw at it, says Shipman. The more cells that are sampled, the better the reconstruction of the data. Fortunately, with modern sequencing tools, reconstruction is quick.

The five frames of a horse in motion showed that it is possible to capture data chronologically and replay them as a video. You get a physical record of events over time, says Shipman. For a long time we wanted to have some way of storing timing information inside cells, says Shipman. The CRISPR system is perfectly adapted to that.

This is a really neat paper, says Yaniv Erlich at Columbia University in New York. The team didnt store that much data and it is not clear that the CRISPR technique can compete with the storage capacity of synthetic DNA. But inserting information into living cells opens up a lot of possibilities, he says.

For a start, it lets you add to or change the stored information later. And because the data is written into the bacterial genomes, it gets passed down between generations. Mutations happen, but not nearly as many as you think, says Shipman certainly not enough to corrupt the data stored across a large population of cells.

Storing data in bacteria could even be a way to make important information survive a nuclear apocalypse. You could useDeinococcus radiodurans, a species that maintains its genome in extreme radiation conditions, says Erlich.

Shipman wants to turn cells into recording devices that document what takes place inside themselves. He is excited about the possibility of keeping a log book of events inside a living brain as it develops, showing how different brain cells acquire their distinct identities.

Its hard to understand what events make brain cells fully defined, says Shipman. You cant easily get in there to take a look. Taking a brain apart disrupts the whole process.

You could also get a cell to diarise what happens as it changes from healthy to diseased. Now that would be an account worth reading.

Journal reference: Nature, DOI: 10.1038/nature23017

More on these topics:

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The Bone Marrow and Stem Cell Transplant Center at the UNM Comprehensive Cancer Center offers treatment choices for people with lymphoma and myeloma.Almost 1,000 New Mexicans receive a blood cancer diagnosis each year, according to American Cancer Society estimates.

The UNM Comprehensive Cancer Center program is the states only bone marrow transplant program.It includes a nurse manager, nurse coordinator, a social worker, a pharmacist, infusion nurses, and an inpatient team. Bone marrow transplantation needs a multidisciplinary team because of the complexity in coordinating care, says Fero. The teams Nurse Manager, Maria Limanovich, says the team follows each person from the beginning of bone marrow transplant treatment through completion.

Bone marrow, the soft reddish material that fills the inside of our bones, produces millions of new blood cells each second. These millions of cells come from a tiny number of bone marrow stem cells. These stem cells are special because they can mature into all of the different types of cells in the blood. These are the cells doctors collect for a transplant.

Autologous bone marrow transplants are standard treatments for lymphoma and myeloma.

Matthew Fero, MD, FACPBone Marrow Stem Cell Program Director

Because bone marrow is a liquid organ, Fero says, it can pass through an IV [intravenous] line. Doctors rarely need to take stem cells directly out of the bone, Fero explains. They use drugs to coax bone marrow stem cells into the bloodstream. From there, the blood travels through an IV line into an apheresis machine that sorts the stem cells out and returns the rest of the blood. The experience is like donating blood at a blood bank.

Once stem cells are safely stored out of the bloodstream, doctors use high-dose chemotherapy to eradicate the remaining cancer. When chemotherapy is out of their system, the patients stem cells are reinfused. The process is similar to blood transfusion. Stem cells find their way back to bone marrow where they begin to grow and make new blood cells.

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Hypogonadism is the underproduction of sex hormones by the gonads, or sex organs. Male hypogonadism refers to the underproduction of testosterone, which can severely limit a growing boys sexual development and frustrate an adult males quality of life.

The easiest way to understand the effects of hypogonadism is to understand the effects of proper testosterone levels in a mans development. The male sex hormone contributes to everything from the deepening of the voice, the growth of body hair, and muscle building to sex drive and general self confidence. A lack of testosterone has the opposite effect, and can contribute to a higher-pitched voice, loss of body hair, muscle loss, lowered sex drive, and decreased confidence.

Hypogonadism can occur as early as fetal development, which may lead to androgyny, but male hypogonadism in particular can also occur as a result of testicular injury. Hypogonadism sustained before puberty is particularly problematic, as it will greatly affect puberty. Low testosterone during puberty can lead to:

Hypogonadism that occurs after puberty is less obvious, but can also lead to major problems, such as:

While these are some of the physical symptoms of hypogonadism, it is worth noting that hypogonadism, no matter when it occurs, can also lead to persistent psychological and emotional duress. Common stressors that accompany male hypogonadism may include:

Areas Low Testosterone Can Affect

Many adult males who have gone through puberty normally but experience hypogonadism in later life may not recognize its symptoms. If you suspect that you may be suffering from hypogonadism, testosterone replacement therapy is a potential treatment option. The pervasive symptoms of hypogonadism are caused in large part by low testosterone, and testosterone replacement therapy can greatly improve quality of life and sex drive.

Dr. Olivieri has many decades of experience treating men with low testosterone, and has helped thousands of men experience the benefits of normal testosterone levels, improving their lives, marriages, and mobility. If you know someone who may be suffering from hypogonadism or low testosterone in general, consider calling Aegonics Medical for a consultation.

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Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM, Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010; 95(6): 2536-59. PubMed

Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Sep 2017]

Dean JD, McMahon CG, Guay AT, Morgentaler A, Althof SE, Becher EF, Bivalacqua TJ, Burnett AL, Buvat J, Meliegy AE, Hellstrom WJ, Jannini EA, Maggi M, McCullough A, Torres LO, Zitzmann M. The International Society for Sexual Medicine's Process of Care for the Assessment and Management of Testosterone Deficiency in Adult Men. J Sex Med. 2015; 12(8): 1660-86. PubMed

Dohle G, Arver S, Bettocchi C, et al. Guidelines on male hypogonadism. European Association of Urology. Arnhem (the Netherlands) [Accessed: Jun 2017]

Kushnir MM, Blamires T, Rockwood AL, Roberts WL, Yue B, Erdogan E, Bunker AM, Meikle W. Liquid chromatography-tandem mass spectrometry assay for androstenedione, dehydroepiandrosterone, and testosterone with pediatric and adult reference intervals. Clin Chem. 2010; 56(7): 1138-47. PubMed

Morales A, Bebb RA, Manjoo P, Assimakopoulos P, Axler J, Collier C, Elliott S, Goldenberg L, Gottesman I, Grober ED, Guyatt GH, Holmes DT, Lee JC, Canadian Mens Health Foundation Multidisciplinary Guidelines Task Force on Testosterone Deficiency. Diagnosis and management of testosterone deficiency syndrome in men: clinical practice guideline. CMAJ. 2015; 187(18): 1369-77. PubMed

Paduch DA, Brannigan RE, Fuchs EF, Kim ED, Marmar JL, Sandlow JI. The laboratory diagnosis of testosterone deficiency. Urology. 2014; 83(5): 980-8. PubMed

Seftel AD, Kathrins M, Niederberger C. Critical Update of the 2010 Endocrine Society Clinical Practice Guidelines for Male Hypogonadism: A Systematic Analysis. Mayo Clin Proc. 2015; 90(8): 1104-15. PubMed

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Hypogonadism, Male | ARUPConsult Lab Test Selection

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The application cycle is now open.

The Physician-Scientist Career Development Award provides an opportunity for first-, second-, and third-year medical students to gain experience in hematology research under the mentorship of an ASH member and to learn more about the specialty. Awardees must agree to spend more than 80 percent of their time, during the immersive, year-long project, conducting laboratory, translational, or clinical hematology research.

The award provides recipients with $42,000 of funding for a one-year period. This includes $32,000 to support the trainee, $4,000 for research supplies, $4,000 for insurance and educational expenses (including one course), and $2,000 for meeting attendance (including the ASH annual meeting).

Award recipients attend the ASH annual meeting in December following their research experience. During an orientation breakfast, members of the ASH Committee on Training and Trainee Council are available to discuss specific areas of research and to provide recommendations on annual meeting sessions, events, abstracts, and/or posters related to the awardees areas of interest. Awardees are also invited to attend the Career Development Reception on Monday evening.

Jump To:

SelectTimelineEligibility RequirementsApplication ProcessEvaluation, Selection, and NotificationTerms and Conditions Questions

At the time of application, the applicant must:

The following individuals are not eligible to apply:

Physician-Scientist Career Development Award mentors must be ASH members who will assume the responsibilities of overseeing the award recipients work and progress. Mentors assist in completing the program application, aid the recipient in his/her research, and ensure that the recipient meets all deadlines, including those for award reports.

ASH believes that a multiple mentorship model is important for researchers regardless of their career stage. Therefore, the applicant may include a second mentor in his/her application to provide advice and career development support as well as additional guidance on research questions. If the study section believes additional mentorship may be beneficial to the applicant, members of the study section will be responsible for identifying an appropriate mentor and facilitating contact. The additional mentor will coordinate with the research mentor to the extent that is feasible and desirable.

The Physician-Scientist Career Development Award application, as well as all supporting documents outlined below, must be submitted through the ASH online awards system.

Required Documents

For more information about the required materials, please see the Required Documents PDF.

Applications submitted by the deadline will be reviewed by the Physician-Scientist Career Development Award study section. Applicants will be evaluated on the following criteria:

There is no limit to the number of applications that an institution and its affiliates can submit. However, no more than one award will be granted for any given institution. For this purpose, ASHs definition of medical school encompasses all affiliate institutions (e.g., University of Washington would include the Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, etc.).

All awards will be activated on July 1 of the award year and will conclude on June 30 of the following year (off-cycle exceptions may be allowed with explanation). Payment will be made in two equal installments (on July 1 and on January 1) to the institution at which the recipient will conduct his/her research. Research award funds are non-transferable.

As a condition of acceptance of the Physician-Scientist Career Development Award, it is required that:

After the award period, recipients are required to submit a final written report (not to exceed four pages). The report will include a summary of research, manuscript submissions during the award period related to the funded research, presentations (locally and nationally) of the funded research during the award period, educational goals met, and a summary of the usage of funds. This report must be emailed to awards@hematology.org. Members of the Oversight Committee will evaluate final reports.

Please note: Failure to submit the final report or an interim progress report will render the applicant ineligible for future ASH funding.

Students making significant progress may submit a written request to reapply for one additional year of funding. Award renewal requests should be submitted by the award deadline. As part of the request, a joint letter must be submitted by the awardee and his/her mentor addressing the following:

No-cost extensions may be requested if needed. To request an extension, the awardees mentor should submit a letter to ASH by emailing the Awards Department at awards@hematology.org.

Any funding not spent by the end of the award term must be returned to the Society when submitting the final report. A check made out to American Society of Hematology must be sent to the address listed below:

Allie SamisAwards Programs SpecialistAmerican Society Hematology2021 L Street NW, Suite 900Washington, DC 20036

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ASH Physician-Scientist Career Development Award

Recommendation and review posted by simmons

CRISPR, a new genome editing tool, could transform the field of biologyand a recent study on genetically-engineered human embryos has converted this promise into media hype. But scientists have been tinkering with genomes for decades. Why is CRISPR suddenly such a big deal?

The short answer is that CRISPR allows scientists to edit genomes with unprecedented precision, efficiency, and flexibility. The past few years have seen a flurry of firsts with CRISPR, from creating monkeys with targeted mutations to preventing HIV infection in human cells. Earlier this month, Chinese scientists announced they applied the technique to nonviable human embryos, hinting at CRISPRs potential to cure any genetic disease. And yes, it might even lead to designer babies. (Though, as the results of that study show, its still far from ready for the doctors office.)

In short, CRISPR is far better than older techniques for gene splicing and editing. And you know what? Scientists didnt invent it.

CRISPR is actually a naturally-occurring, ancient defense mechanism found in a wide range of bacteria. As far as back the 1980s, scientists observed a strange pattern in some bacterial genomes. One DNA sequence would be repeated over and over again, with unique sequences in between the repeats. They called this odd configuration clustered regularly interspaced short palindromic repeats, or CRISPR.

This was all puzzling until scientists realized the unique sequences in between the repeats matched the DNA of virusesspecifically viruses that prey on bacteria. It turns out CRISPR is one part of the bacterias immune system, which keeps bits of dangerous viruses around so it can recognize and defend against those viruses next time they attack. The second part of the defense mechanism is a set of enzymes called Cas (CRISPR-associated proteins), which can precisely snip DNA and slice the hell out of invading viruses. Conveniently, the genes that encode for Cas are always sitting somewhere near the CRISPR sequences.

Here is how they work together to disable viruses, as Carl Zimmer elegantly explains in Quanta:

As the CRISPR region fills with virus DNA, it becomes a molecular most-wanted gallery, representing the enemies the microbe has encountered. The microbe can then use this viral DNA to turn Cas enzymes into precision-guided weapons. The microbe copies the genetic material in each spacer into an RNA molecule. Cas enzymes then take up one of the RNA molecules and cradle it. Together, the viral RNA and the Cas enzymes drift through the cell. If they encounter genetic material from a virus that matches the CRISPR RNA, the RNA latches on tightly. The Cas enzymes then chop the DNA in two, preventing the virus from replicating.

There are a number Cas enzymes, but the best known is called Cas9. It comes from Streptococcus pyogenes, better known as the bacteria that causes strep throat. Together, they form the CRISPR/Cas9 system, though its often shortened to just CRISPR.

Top image: Screenshot from this MIT video explaining CRISPR

As this point, you can start connecting the dots: Cas9 is an enzyme that snips DNA, and CRISPR is a collection of DNA sequences that tells Cas9 exactly where to snip. All biologists have to do is feed Cas9 the right sequence, called a guide RNA, and boom, you can cut and paste bits of DNA sequence into the genome wherever you want.

DNA is a very long string of four different bases: A, T, C, and G. Other enzymes used in molecular biology might make a cut every time they see, say, a TCGA sequence, going wild and dicing up the entire genome. The CRISPR/Cas9 system doesnt do that.

Cas9 can recognize a sequence about 20 bases long, so it can be better tailored to a specific gene. All you have to do is design a target sequence using an online tool and order the guide RNA to match. It takes no longer than few days for the guide sequence to arrive by mail. You can even repair a faulty gene by cutting out it with CRISPR/Cas9 and injecting a normal copy of it into a cell. Occasionally, though, the enzyme still cuts in the wrong place, which is one of the stumbling blocks for wider use, especially in the clinic.

Mice whose genes have been altered or knocked out (disabled) are the workhorses for biomedical research. It can take over a year to establish new lines of genetically-altered mice with traditional techniques. But it takes just few months with CRISPR/Cas9, sparing the lives of many mice and saving time.

Traditionally, a knockout mouse is made using embryonic stem (ES) cells. Researchers inject the altered DNA sequence into mouse embryos, and hope they are incorporated through a rare process called homologous recombination. Some of first generation mice will be chimeras, their bodies a mixture of cells with and without the mutated sequence. Only some of the chimeras will have reproductive organs that make sperm with mutated sequence. Researchers breed those chimeras with normal mice to get a second generation, and hope that some of them are heterozygous, aka carrying one normal copy of the gene and one mutated copy of the gene in every cell. If you breed two of those heterozygous mice together, youll be lucky to get a third generation mouse with two copies of the mutant gene. So it takes at least three generations of mice to get your experimental mutant for research. Here it is summarized in a timeline:

But heres how a knockout mouse is made with CRISPR. Researchers inject the CRISPR/Cas9 sequences into mouse embryos. The system edits both copies of a gene at the same time, and you get the mouse in one generation. With CRISPR/Cas9, you can also alter, say, fives genes at once, whereas you would have to had to go that same laborious, multi-generational process five times before.

CRISPR is also more efficient than two other genome engineering techniques called zinc finger nuclease (ZFN) and transcription activator-like effector nucleases (TALENs). ZFN and TALENs can recognize longer DNA sequences and they theoretically have better specificity than CRISPR/Cas9, but they also have a major downside. Scientists have to create a custom-designed ZFN or TALEN protein each time, and they often have to create several variations before finding one that works. Its far easier to create a RNA guide sequence for CRISPR/Cas9, and its far more likely to work.

Most science experiments are done on a limited set of model organisms: mice, rats, zebrafish, fruit flies, and a nematode called C. elegans. Thats mostly because these are the organisms scientists have studied most closely and know how to manipulate genetically.

But with CRISPR/Cas9, its theoretically possible to modify the genomes of any animal under the sun. That includes humans. CRISPR could one day hold the cure to any number of genetic diseases, but of course human genetic manipulation is ethically fraught and still far from becoming routine.

Closer to reality are other genetically modified creaturesand not just the ones in labs. CRISPR could become a major force in ecology and conservation, especially when paired with other molecular biology tools. It could, for example, be used to introduce genes that slowly kill off the mosquitos spreading malaria. Or genes that put the brakes on invasive species like weeds. It could be the next great leap in conserving or enhancing our environmentopening up a whole new box of risks and rewards.

With the recent human embryo editing news, CRISPR has been getting a lot of coverage as a future medical treatment. But focusing on medicine alone is narrow-minded. Precise genome engineering has the potential to alter not just us, but the entire world and all its ecosystems.

More Reading:

Breakthrough DNA Editor Borne of Bacteria Quanta, Carl Zimmer

A CRISPR For-CAS-t The Scientist, Carina Storrs

Genetically Engineering Almost Anything NOVA NEXT, Tim De Chant and Eleanor Nelsen

This post has been updated to clarify that the the number of basepairs in guide RNA for CRISPR/Cas9 is different from the number of basepairs it recognizes in a target sequence.

Contact the author at sarah@gizmodo.com.

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Everything You Need to Know About CRISPR, the New Tool that ...

Recommendation and review posted by Bethany Smith

Nov. 14, 2011 -- The first use of heart stem cells in humans looks like a major breakthrough for people suffering heart failure after heart attacks.

It's early -- results are in for only the first 16 patients -- but the results already are drawing praise from experts not easily impressed by first reports.

"This is a groundbreaking study of extreme importance," Joshua Hare, MD, director of the University of Miami's Interdisciplinary Stem Cell Institute, tells WebMD via email. Hare was not involved in the study.

"The reported benefits are of an unexpected magnitude," writes Gerd Heusch, MD, PhD, chair of the Institute of Pathophysiology at the University of Essen, Germany, in an editorial in the Nov. 14 online issue of The Lancet.

Study researcher John H. Loughran, MD, of the University of Louisville, Ky., could barely contain his excitement in an interview with WebMD.

"The improvement we have seen in patients is quite encouraging," he says. "Michael Jones, our first patient, could barely walk 30 feet [before treatment]. I saw him this morning. He says he plays basketball with his granddaughter, works on his farm, and gets on the treadmill for 30 minutes three times a week. It is stories like that that makes these results really encouraging."

The breakthrough comes just as researchers were becoming discouraged by studies in which bone-marrow stem cells failed to heal damaged hearts.

Instead of getting stem cells from the bone marrow, the new technique harvests stem cells taken from the patients' own hearts during bypass surgery. Just 1 gram of heart tissue -- about 3.5 hundredths of an ounce -- is taken.

Using a technique invented by Brigham & Women's Hospital researchers Piero Anversa, MD, and colleagues, heart stem cells are taken from the tissue and grown in the lab. These adult stem cells already are committed to becoming heart cells, but they can transform into any of the three different kinds of heart tissues.

It's the first time tissue-specific stem cells, other than bone-marrow cells, have been tested in humans, Hare says.

In the study, about a million of the cells were infused into each patient's heart with a catheter. Calculations suggest that each of these infused cells could generate 4 trillion new heart cells.

The study was designed to show whether the technique was safe. It was: No harmful effects have been seen. But to the researchers' surprise, the relatively small number of cells infused into patients had a major effect.

Of the 14 patients analyzed so far, heart function improved dramatically. And in the eight patients seen one year after treatment, improvement appears to have continued. Moreover, the scars on patients hearts -- areas of dead tissue killed during their heart attacks -- are healing.

And patients aren't just doing better on measures of heart function. Like Michael Jones, they report vastly improved quality of life and ability to perform daily tasks.

"Now this is an open-label trial, so patients know they are treated. This means we have to take what they say with a grain of salt," Loughran says. "But we see these patients not only are feeling better but doing more."

The only downside of this early success is that the ongoing study already has enrolled all 20 of the patients who will be treated. The experimental treatment simply will not be available to other patients in the near future. A larger, phase II study is planned.

"All the patients that call in to us, and there are quite a few interested, we encourage them to maintain close contact with their doctors," Loughran says. "Lifestyle changes and medical management are the most important things for them right now. We will be working very hard to get new trials under way."

The findings were reported at the American Heart Associations Scientific Sessions meeting in Orlando, Fla., and in the Nov. 14 online edition of The Lancet.

SOURCES:

John H. Loughran, MD, fellow in cardiovascular medicine, University of Louisville, Ky.

Joshua Hare, MD, director, Interdisciplinary Stem Cell Institute, University of Miami.

Bolli, R. The Lancet, published online Nov. 14, 2011.

Heusch, G. The Lancet, published online Nov. 14, 2011.

Traverse, J.H. Journal of the American Medical Association, published online Nov. 14, 2011.

Hare, J. Journal of the American Medical Association, published online Nov. 14, 2011.

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Stem Cells Repair Heart in First-Ever Study - webmd.com

Recommendation and review posted by simmons

Agriculture has come a long way in the past century. We produce more food than ever before but our current model is unsustainable, and as the worlds population rapidly approaches the 8 billion mark, modern food production methods will need a radical transformation if theyre going to keep up. But luckily, theres a range of new technologies that might make it possible. In this series, well explore some of the innovative new solutions that farmers, scientists, and entrepreneurs are working on to make sure that nobody goes hungry in our increasingly crowded world.

Corn isnt the sexiest crop but its one of the most important. Its the most abundant grain on Earth, used as food and biofuel around the globe. In ancient times, Mesoamericans thrived on it, waged wars over it. Their myths claimed corn was the matter from which gods created mankind itself.

But, just as corn helped create these civilizations, these civilizations helped create corn through meticulous selective breeding. Todays grain hardly resembles its ancestors. Compared to the wild plant first cultivated by ancient Mexicans some ten thousand years ago, modern corn is a super mutant.

And yet, after all those thousands of years of cultivation, just two main genes are thought to be responsible for the evolution of the corn we eat today. Selective breeding is painstakingly slow and imprecise.

But thats all about to change.

Selective breeding is painstakingly slow and imprecise. But thats all about to change.

New gene editing tools like CRISPR/Cas9 now let scientists hack into genomes, make precise incisions, and insert desired traits into plants and animals. Well soon have corn with higher crop yields, mushrooms that dont brown, pigs with more meat on the bone, and disease resistant cattle. Changes that took years, decades, or even centuries, can now be made in a matter of months. In the next five years you might eat tortilla chips made from edited corn. By 2020 you might drink milk from an edited cow.

Dubbed the CRISPR Revolution these scientific advances in gene editing have huge potential that many experts think could help fortify our food system and feed an increasing population of farmers who are threatened by food scarcity caused, in part, by climate change.

But not everyone is so certain. Beyond the contentious legal battles that have thus far complicated CRISPR science, calling into question who can and cant use the technology, some consumer rights advocates think these tools will be used to maintain the status quo of an industry based primarily on corporate profit. Meanwhile, residual worry about genetically modified organisms (GMOs) may influence the public perception of gene-edited organisms, steering consumers towards the organic aisle despite scientific evidence.

Gene editing is, simply put, the act of making intentional changes to DNA in order to create an organism with a specific trait or traits. Its like using a word processor to edit the words in a sentence. Geneticists insist we dont confuse this with genetic modification (otherwise called genetic engineering), which introduces new genes from different species in order to achieve desired traits. The difference may sound trivial but experts say it could help calm the concerns associated with GMOs.

Consider this simplification. We have the sentence, The cat has a hat, but want to be more descriptive about the hats color. With modification, we would borrow the German word for black and write, The cat has a schwarz hat. The sentence makes sense (sort of) but its obvious that to some people it would be problematic and maybe even an improper use of language. With editing, we dont have to borrow a word from another language. We instead just insert the English word and write, The cat has a black hat.

In the older, more traditional system, scientists were taking a gene from one species and putting it into a plant to confer a particular trait on that plant, Rachel Haurwitz, co-founder of Caribou Biosciences, told Digital Trends. Thats not what were looking to do. Were looking to use CRISPR gene editing to achieve the same outcome as we can get from traditional breeding, just faster.

This ability to edit with such speed and precision is still relatively new, and due largely to CRISPR, which emerged straight from nature to become the most popular and powerful gene editing tool used today. Discovered in bacteria in the late eighties, it wasnt until 2005 that researchers began to unravel its role. Scientists found that when certain bacteria come under attack from viruses, they use special enzymes to cut, copy, and save a bit of the viral DNA. Later, if the intruder returns, the bacteria can quickly recognize it and react to defend itself.

A few years later, researchers realized this system could be used to cut and edit the DNA of any organism, not just viruses. In 2012, Jennifer Doudna and Emmanuelle Charpentier published the first paper demonstrating how CRISPR can be used to edit an organisms genome.

Were looking to use CRISPR gene editing to achieve the same outcome as we can get from traditional breeding, just faster.

Not only is this technique far cheaper, faster, and more precise than conventional genetic modification, it avoids many (if not all) of the issues raised by skeptics, whose main concerns point toward the creation of transgenic organisms.

But, whereas genetic modification entails combining DNA from multiple species, gene editing entails altering the DNA of one species with a trait that already exists naturally.

Gene editing is not at all about taking DNA from a foreign species and integrating it into a plant, Haurwitz said. Its really about working within the constraints of the plants own genome.

Just over four years ago, Haurwitz founded Caribou as a spin off from Doudnas lab at the University of California, Berkeley. Since then, her team has partnered with companies around the world, providing licensing rights to use the startups version of the gene editing tool. One of those partnerships may see the first CRISPR-edited organism come to market via DuPont Pioneer, one of the worlds biggest chemical companies.

The day before Halloween 2015, Yinong Yang submitted an Am I Regulated letter to the United States Department of Agricultures (USDA) Animal and Plant Health Inspection Service (APHIS). He and his colleagues at Penn State had used CRISPR to knock out a gene in white button mushrooms that makes them go brown over time. Without the browning gene, white buttons look better and last longer, and Yang wanted to know whether his mushrooms could legally go to market.

The following spring, the departments response resonated throughout the scientific and agricultural community. APHIS does not consider CRISPR/Cas9-edited white button mushroomsto be regulated, it wrote in an open letter.

Last year, researchers at DuPont Pioneer, the agriculture branch of the multi-billion-dollar conglomerate DuPont, published a study about a strain of corn engineered with CRISPR to be more resistant to drought. Its one of several CRISPR-modified crops that may soon be coming to market.

It was a landmark decision. Yangs mushrooms were the first gene-edited crop cleared for commercial sale by the USDA, which made a clear distinction between genetic modification and gene editing, and set a precedent for those to come.

A few days later, DuPont the fourth largest chemical corporation in the world received a similar response from the USDA regarding its CRISPR-edited waxy corn thats disease resistant and drought tolerant. DuPont wasted no time announcing plans to take its crop to market within the next five to ten years.

The USDA has said these products do not fall into their remit, as their remit is really focused on, say, plant pathogens or noxious weeds, said Haurwitz, whose company provides DuPont with its CRISPR technology. At the same time were seeing the FDA put out a call for information as theyre looking at their own remit to oversee the entire food supply, not just products made with modern biotechnology. And I think theyre looking to members of the scientific and business communities to really weigh in over the next few months.

Unlike most Button mushrooms, these ones dont brown or develop blemishes from being handled. This trait doesnt occur naturally it happens because the gene that makes the mushrooms turn brown was selectively removed from them via the CRISPR/Cas9 method. (Photo: Yang Lab)

For Yangs part, he intends to improve his mushrooms before making them commercially available. Although not legally required, he plans to seek approval from the Food and Drug Administration (FDA) and Environmental Protection Agency (EPA).

Edited waxy corn may find its way into the food system much sooner than white button mushrooms, if not as human food than as fodder for the growing number of livestock around the world. Meanwhile, these livestock are also undergoing genetic edits as researchers use the same tools to make animals healthier, meatier, and more productive.

Pigs harbor a lot of diseases and there are few as bad as porcine reproductive and respiratory syndrome (PRRS). It causes pregnant mothers to miscarry and makes it difficult for piglets to breathe. Its a problem for the pig farmers as well. Every year, the PRRS virus costs the industry nearly $1.6 billion dollars in Europe and another $664 million in the US.

The impacts of the disease for producers are often devastating, said Jonathan Lightner, Chief Scientific Officer at biotech company Genus. And the impacts on the animals themselves are terrible.

If we could integrate the polled phenotype into the dairy system, that would eliminate dehorning for at least seven or eight million animals a year.

But Lightner and his team are working on a solution. In December 2015, scientists at Genus and the University of Edinburghs Roslin Institute demonstrated how CRISPR could remove the CD163 molecule, a pathway through which the PRRS virus infects pig. Just last month, the researchers refined their work to remove just the portion of the gene that directly interacts with the virus. Lab tests, as published in a paper in the journal PLOS Pathogens, have shown that DNA in cells removed from these pigs successfully resist the virus. Next steps in the study will test whether the pigs themselves are resistant to the virus.

Swine are also the subject of research at Seoul National University in South Korea, where scientists led by Jin-Soo Kin are using a different gene-editing tool called TALEN to create meatier, double muscle pigs by removing a gene that inhibits muscle growth. We could do this through breeding, Kin told Nature back in 2015, but then it would take decades.

In fact, farmers have developed similar traits through breeding Belgian Blues, a type super-sculpted beef cattle prized for its lean meat and beefy build. It took over a hundred years to establish those traits in the breed.

Researchers at University of California, Davis and a startup called Recombinetics are using the same TALEN gene editing technique to cut decades down to days, removing the horned gene from common dairy cows and inserting the one that makes Angus beef cattle naturally dehorned or polled. Polled cattle are desirable because they pose less threat to their handlers and to each other. But, as Tad Sonstegard, Chief Science Officer of Acceligen (a Recombinetics subsidiary) explained, polled cattle in certain breeds are simply less productive.

Gene editing ala CRISPR/Cas9 has allowed scientists to not only produce polled (hornless) cows, but also cows that are immune to common diseases, such as tuberculosis. (Photo: Gregory Urquiaga/UC Davis)

The issue is that the top [dairy] bulls that everyone wants are horned, Sonstegard said. The animals that are polled that already exist have a difference of about $250 over their lifetime. If youre running a thousand head dairy [operation], thats a lot of money.

What many ranchers do instead is dehorn their cattle, a stressful practice when anesthesia is used, a painful practice when it isnt, and a significant expense for the ranchers either way.

If we could integrate the polled phenotype into the dairy system, that would eliminate dehorning for at least seven or eight million animals a year, Sonstegard said. If you include beef, thats up to fifteen million.

Recombinetics has already bred a couple gene-edited calves, which are undergoing care and monitoring at UC Davis. But, before any gene-edited cows produce the milk in our grocery stores, Sonstegard said scientists would need to prove that milk from these cows is similar to horned and polled cows that havent been gene edited. That would be simple though, he said, it would turn out the same.

As the global population grows, so does the demand for food. Meanwhile, farmers around the world face food scarcity generated in part by a changing climate that makes caring for plants and livestock an increasingly difficult task.

But CRISPR-like tools may be able to help.

On the plant side were looking at ways to breed plants that are more drought tolerant or in other ways can better survive the stresses of climate change, Haurwitz said. I think thats incredibly valuable and important as we look at the exploding global population. Caribou has also partnered with Genus in its project to breed PRRS virus resistant pigs.

Beyond his work at Recombinetics, Sonstegard sits on the scientific advisory board of the Centre for Tropical Livestock Genetics and Health, a Gates Foundation-backed initiative to improve the genetics of native livestock in tropical regions. Most productive livestock breeds cant survive the heat or diseases present in tropical environments, and breeds native to tropical environments havent had the same selective breeding programs that generate highly productive livestock.

Will CRISPR be used primarily for patenting foods in ways that fit in existing corporate profit models?

Most of the indigenous animals have not been under strict artificial selection, Sonstegard said. Its all been done anecdotally, since most farmers dont have that many cows and their systems arent that big. Meanwhile, most of the new DNA introduced to these herds is left over semen from bulls in developed countries, according to Sonstegard. Its cheap, he said, and no one in the developed country wants it anymore, so they ship it overseas.

There are a couple possible approaches to strengthening these indigenous breeds. One way would be to edit the DNA of bulls from productive breeds so that theyre more temperature tolerant and disease resistant within tropical climates. Those bulls could then be introduced to the native herds to reproduce and spread their productive genes. Alternatively, the DNA of indigenous bulls could be edited with genes likely to improve productivity of the herd, including milk production and carcass yield.

Right now the trend in those countries is that theres a linear growth in livestock numbers, Sonstegard said, because theyre not improving production but demand is increasing, so they just make more animals.Thats not sustainable.

Researchers are also using CRISPR to save dying and endangered species. This month some of Sonstegards colleagues published a paper showing they could develop surrogate hens that could help raise endangered species of birds. And in Florida, where an invasive disease known as citrus greening is decimating the states iconic orange industry, University of Florida scientists are using CRISPR to develop varieties of orange trees immune to the disease, according to the Tampa Bay Times.

But not everybody is so gung-ho.

UC Davis geneticist Alison Van Eenennaam, who collaborates with Recombinetics on gene-editing polled cows, is absolutely optimistic about the tool I think it can be used for very useful things, she said. Rather than ask why we should use, lets ask how. but shes also careful not to overstate the potential of gene editing. When asked whether the technology could be used to address world hunger, she said, I kind of think that idea is polyamorous. Show me anything that can magically solve world hunger. Lets not oversell this technology. Its useful but its useful for a fairly discreet purpose at this stage, which is making edits to a [gene] sequence that we know has a particular effect.

And CRISPR, of course, has its skeptics. Stacy Malkan, Co-Director of U.S. Right to Know, a nonprofit that calls for transparency and accountability in the food system, is both concerned about the inherent risk involved in gene editing and suspects it could ultimately perpetuate an already imbalanced food system.

Theres really no big difference between [gene editing] and conventional breeding.

Will CRISPR be used primarily for the purpose of patenting foods in ways that fit in existing corporate profit models, she asked, for example, to engineer commodity crops to withstand herbicides, or to engineer livestock to fit better in unhealthy confined feeding operations? Or will it be used to engineer foods that have consumer benefits? Will there be labeling, and safety assessments? There are many questions. Right now we hear a lot of marketing hype about possible benefits of CRISPR, but we heard the same promises about first-generation GMOs for decades and most of those benefits have not panned out.

For scientists like Van Eenennaam, the GMO discussion is over. Frankly, she said, Im over the debate. If someone isnt convinced by the evidence that every single major scientific society in the world says its safe, than nothing Im going to say is going to convince them any differently. When it comes to gene-edited organisms, most scientists are even more insistent about its safety. Theres really no big difference between [gene editing] and conventional breeding, Van Eenennaam added.

But there isnt complete consensus. Malkan points to an interview she recently had with Michael Hansen, senior scientist from Consumers Union, in which Hansen said of CRISPR-like gene editing tools, These methods are more precise than the old methods, but there can still be off-target and unintended effects. When you alter the genetics of living things they dont always behave as you expect. This is why its crucial to thoroughly study health and environmental impacts, but these studies arent required.

From Sonstegards perspective, mutations and off-target effects occur naturally anyway, and gene editing simply offers a more precise approach than selective breeding.

Still, Malkan and others have their reservations, grounded in the idea that its too early to determine the side effects. CRISPR is a powerful research tool for helping scientists understand genetics, how cells react, how entire plants and systems react, she said. In my view these experimental technologies should be kept in the lab, not unleashed in our food system, until those systems are better understood.

See more here:
CRISPR Gene Editing and the DNA of Future Food | Digital Trends

Recommendation and review posted by sam

CRISPR/Cas9 is a gene editing technology thats revolutionizing science at a breathtaking pace.

One of its most exciting, taboo, and controversial applications is tweaking the genes of eggs, sperm, or early embryos to alter a human life. This could one day mean the ability to create smarter or more athletic humans (yes, designer babies), but also the chance to knock out disease-causing genetic mutations that parents pass on to their children. Were talking about eliminating mutations linked to diseases like breast and ovarian cancers or cystic fibrosis.

On Wednesday, a team of scientists reported that they have made major progress toward proving the latter is possible.

In a paper published in the prestigious journal Nature, a team led by Shoukhrat Mitalipov of Oregon Health and Science University described how it used CRISPR/Cas9 to correct a genetic mutation thats linked to a heart disorder called hypertrophic cardiomyopathy in human embryos. And they did it without the errors that have plagued previous attempts to edit human embryos with CRISPR.

To be clear, the new work from OHSU was an experiment the point was to test a concept, and the embryos used were never implanted into a womans uterus.

But the researchers were ultimately able to show that CRISPR/Cas9 can do what they hoped it would do. It cut the mutant gene sequence, prompted the embryos to repair the DNA with healthy copies of the gene, and eliminated the disease-causing mutation altogether from many of the embryos.

Lets pause for a minute and make sure were clear on what CRISPR/Cas9 is. You can read our full explainer here, but in a nutshell, its essentially a clever system built into bacterial DNA that allows them to recognize and fend off attackers, usually viruses. The way it works, as Brad Plumer described it, is that special enzymes in the CRISPR sequences known as Cas9 carry around stored bits of viral genetic code like a mug shot. When they find a match to the code, they will chop up the DNA and neutralize the threat.

The real breakthrough, which appeared in a series of landmark papers published in 2012 and 2013, was figuring out that it was possible to program CRISPR/Cas9 to find any kind of DNA code, not just viruses, and get the enzymes to snip it.

Mitalipov and colleagues created embryos in the lab with sperm from a carrier of the disease-causing mutation in the MYBPC3 gene, and eggs from 12 healthy donors. And they sent CRISPR/Cas9 into the fertilized egg.

As the embryos developed, they found that after CRISPR/Cas9 cut the sequence in the embryo DNA with the problematic gene. In most cases the embryos repaired the breaks with a healthy copy of the gene from the maternal donor.

In all, 36 out of 54 embryos ended up with mutation-free copies of MYBPC3. (Another, slight different round of the experiment yielded 42 out of 58 embryos with mutation-free copies of the gene.) Which means that had those embryos become children, the children would have had practically no chance of developing hypertrophic cardiomyopathy. Thats pretty significant since this a disease that affects one in 500 people and can cause sudden cardiac death and heart failure. If one parent has a mutant copy of MYBPC3, their child has a 50 percent chance of inheriting the condition.

These results are also promising for people (mainly older women and couples) who have a limited number of viable embryos to use to get pregnant with in vitro fertilization. Currently, reproductive medicine doctors use something called preimplantation genetic diagnosis, or PGD, to identify embryos with harmful mutations. And when they find embryos with mutations linked to disease, they often discard them, which can leave patients with few healthy embryos to try to transfer into the womb. (Transfer success rates are overall pretty low.)

The researchers say that in the future, their technique could be used with PGD to help fix the mutations in embryos that otherwise would be discarded, giving women and couples more embryos to transfer and a better chance of getting pregnant.

Were not ready for gene editing in embryos that would be implanted for pregnancy anytime soon. But this is a big advance because the researchers got stronger results than anyone who has ever tried to target disease-causing genes with CRISPR-Cas9 before.

And while the experiment focused only on this particular gene and disease, the researchers say they feel confident the technique would work for many of the thousands of other inherited disorders out there linked to one mutation because their approach has so far proved to be efficient, accurate, and safe.

But in a press conference on Tuesday, one of the co-authors, Paula Amato, an OB-GYN doctor at OHSU, stressed that many more safety tests would be needed before proceeding with a clinical trial. We want to replicate the study with other mutations and other [sperm and egg] donors, she said. In particular, she said shes interested in seeing if it works on BRCA1 and 2, mutations that increase the risk of breast and ovarian cancers.

Other researchers, including Nerges Winblad and Fredrik Lanner at Karolinska Institutet in Sweden, who wrote an accompanying article in Nature, are encouraged by the results but still cautious about the safety of the technology. They zeroed in on issues that have shown up in previous studies: off-target effects, or undesirable mutations in genome regions close to the targeted sequence, and mosaicism, where not all embryo cells make the desired changes. According to Winblad and Lanner, researchers will have to keep showing that they can reliably avoid these and other abnormalities in edited embryos before [the technology] can be used as a therapy for inherited diseases.

Amato and her co-authors said theres also plenty of room for other improvement. Some of their embryos DNA ended up with unintended additions or deletions. So their goal would be to get 80 to 90 percent of a large group of embryos mutation-free to ensure that the technique is reliable before attempting a clinical trial.

Again, this wasnt the first time scientists had tried to use CRISPR to edit human embryos. Chinese researchers have done it twice: once in 2015 to modify a gene linked to the blood disorder called beta thalassaemia, and then in 2016 to make genes resistant to HIV. But both of these experiments were smaller, and one used abnormal embryos while the other used immature eggs. And the results from both were messy, suggesting that embryo editing had a long, hard road ahead.

It was precisely those messy results, along with a host of other concerns, that prompted the Organizing Committee for the International Summit on Human Gene Editing at the National Academies of Sciences, Engineering, and Medicine to advise researchers in December 2015 to be extremely cautious about editing sperm, eggs, and embryos (known collectively as the human germline). Then in a report in February, it said clinical trials on human genome editing might one day be allowed, but in the meantime, researchers could attempt to correct mutations that cause a serious disease or condition and only when no reasonable alternatives exist. And definitely no research on enhancement of human traits like intelligence or strength for now.

At present, the US government does not fund any genomic editing of human embryos. (Mitalipov and his colleagues got funding from their university this new study.) And the Food and Drug Administration is prohibited by Congress from considering any clinical trials related to genetic editing of eggs, sperm, or embryos.

The impressive new findings in Nature raise huge questions about how the US should proceed with this field of research. How soon to allow clinical trials, for instance?

I believe [the National Academies] can reconsider what mutations and what cases the gene corrections can be used and must be used to allow clinical trials in the future to go forward, said Mitalipov. We may not be in agreement with the committees. The work is back and forth, and the committees hopefully will consider new options.

He added that hed be willing to move this research to the UK, if necessary. He also is sensitive about how his results are portrayed, given the American publics reticence, and in some cases fear, about genetic modification.

I dont like the word editing, he said. We didnt edit or modify anything. ... We used CRISPR to correct, using existing maternal genes.

Other CRISPR researchers have weighed in about where the field should go from here.

In my opinion, we still need to respect the recommendations in the [National Academy of Sciences] report published in February that recommended refraining from clinical use of human germline editing until and unless theres broad societal consensus about the value, Jennifer Doudna, a UC Berkeley molecular biologist and a leading CRISPR researcher, told the Los Angeles Times.

It may be quite a while before a clinical trial is approved. In the meantime, any prospective parents who want to avoid passing on disease-causing genes to their kids will have to continue to use PGD during in vitro fertilization.

As weve reported, scientists from myriad fields are using CRISPR to try to grow better food, destroy viruses, and clean up the environment.

Hank Greely explains for Vox why in 20 to 40 years, most Americans wont have sex to reproduce.

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Scientists successfully used CRISPR to fix a mutation that ...

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A few years ago, the use of hormone replacement therapy (HRT) looked like a medical mess. For decades, women were told that HRT -- usually a combination of estrogen and progestin -- was good for them during and after menopause. Then the 2002 results of the Women's Health Initiative study seemed to show just the opposite: hormone replacement therapy actually had life-threatening risks such as heart attacks, strokes, and cancer.

"Women felt betrayed," says Isaac Schiff, MD, chief of obstetrics and gynecology at Massachusetts General Hospital in Boston. "They were calling their doctors, saying, 'How could you put me on this drug which causes heart attacks, strokes, and cancer?'"

Almost overnight, standard medical practice changed. Doctors stopped prescribing hormone replacement therapy and 65% of women on HRT quit, according to Schiff.

But some experts say hormone replacement therapy may be coming back. All along HRT remained an important treatment for menopause symptoms like hot flashes. And now, a number of recent studies show that hormone replacement therapy may have protective benefits for women who are early in menopause.

"I think we swung too positive on hormone therapy in the past and then we went too negative," says Schiff, who is also chair of the American College of Obstetricians and Gynecologists Task Force on Hormone Therapy. "Now we're trying to find a balance in between."

"We're definitely in a gray zone of uncertainty about hormone therapy," says Jacques Rossouw, MD, project officer for the federal Women's Health Initiative (WHI). "But when you're uncertain, you have to err on the side of safety."

While Rossouw concedes that new studies show some preventative benefit for younger women, he says any potential benefit is very slight. And, he notes, there is no evidence that any benefit would last if women kept taking hormones as they got older.

But increasing numbers of researchers say there should be a place for hormone replacement therapy as a preventive treatment for limited periods as it may help prevent disease in younger women around the age of menopause.

"We have evidence that hormone therapy can prevent heart disease, hip fractures, and osteoporosis, and that it cuts the risk of developing diabetes by 30% in younger women," says Shelley R. Salpeter, MD, a clinical professor of medicine at Stanford University's School of Medicine.

In one recent study, Salpeter and her colleagues found that HRT reduced the number of heart attacks and cardiac deaths by 32% in women who were 60 or younger (or women who had been through menopause less than 10 years ago). In older women, hormone replacement therapy seemed to increase cardiac events in the first year, and then began to reduce them after two years.

The 32% drop is significant, but perhaps not as dramatic as it sounds. In hard numbers, Salpeter estimates that of women aged 50 to 59 who don't get hormone replacement therapy, about 7 out of 4,800 will have a cardiac event in one year. With HRT, 3 out of 4,800 will have a cardiac event.

Salpeter's study indicates something crucial: The age at which a woman starts HRT may make a big difference.

Salpeter argues that when a person first starts hormone replacement therapy, her risk of blood clots increases slightly. In healthy women who are in their 50s -- and close to the age of menopause -- this increase is very unlikely to cause problems. The higher risk subsides after a couple of years, she says, although other experts disagree.

But women in their 60s may be more likely to already have early heart disease or hardening of the arteries (arteriosclerosis). In these cases, the risk of blood clots becomes more serious. So if a woman first starts hormone replacement therapy in her 60s, the initial risks are more dangerous, Salpeter says.

This is what Salpeter says affected the results of the Women's Health Initiative trial. The average age of a woman in that trial was 63, with a range of ages between 50 and 79. She and other critics argue that the researchers were looking at many women who might already have been sick.

"I was surprised when I first heard the [WHI] results," says Lynne T. Shuster, MD, director of the Women's Health Clinic at the Mayo Clinic in Rochester, Minn. "But, once I saw the details, I wasn't surprised anymore. They gave women who were older and possibly had underlying arteriosclerosis a pill that increased the risk of blood clotting. Of course it increased the risk of heart problems."

Shuster and Salpeter argue that those results have no bearing on whether younger, healthy women in their 50s would benefit from HRT.

"Basically, [the WHI researchers] were looking at the wrong group of people," Salpeter tells WebMD.

Rossouw defends the WHI study design. "We were specifically testing the hypothesis that hormone therapy would help protect older women against disease," Rossouw tells WebMD, "The results were absolutely clear: They do not."

Media reports on the WHI results may have given people inflated fears of hormone replacement therapy's risks, the doctors say.

For example, the Women's Health Initiative results showed that combined hormone replacement therapy seems to increase the risk of breast cancer by 33%, Schiff says. That's a serious increase. Still, the risk to any one woman is not as high as it sounds, Schiff says.

"According to the WHI, without hormone therapy, 3 of every 1,200 women aged 55 to 59 will develop breast cancer this year," says Schiff. "With hormone therapy, 4 out of 1,200 will. It's a 33% increase, but the absolute risk is still very, very small."

Shuster points out that other behaviors -- like drinking two glasses of wine a night -- also increase breast cancer risk by a similar amount.

Women who take estrogen alone -- a treatment only available to people who have had a hysterectomy -- appear to have a lower risk of developing breast cancer than women who take progestin and estrogen together. In a 2006 JAMA article, researchers from the Women's Health Initiative found that after about seven years of treatment with estrogen, there seemed to be no increased risk of breast cancer.

However, estrogen-only therapy may have long-term risks. A May 2006 study published in the Archives of Internal Medicine found using estrogen-only therapy for 20 years or more showed increased risk of developing breast cancer.

As HRT is being re-evaluated -- and new evidence is coming in -- it's difficult to know who should get hormone replacement therapy and for how long.

The U.S. Food and Drug Administration (FDA) recommends that HRT should be used in women who have severe menopausal symptoms.

"Estrogens are the best agents we have for the relief of menopausal symptoms like hot flashes, vaginal dryness, and loss of sexuality," says Schiff. They're also a good treatment for menopausal symptoms that are often not recognized: Difficulty sleeping, stiffness, joint pain, and mood changes.

But for disease prevention -- lowering the risk of heart attacks, strokes, and most cases of osteoporosis -- the FDA still does not recommend hormone replacement therapy.

"We have other ways of cutting the risks of heart attacks and strokes," Schiff tells WebMD, including better diet, exercise, and other medicines.

Will HRT ever again be used as prevention for these serious diseases? Only time and research will tell. The experts remain divided.

"I believe that studies in the next few years will support using hormone therapy in younger women [closer to the onset of menopause] for prevention," says Shuster. "But "we don't have all the information yet."

Another big question is how long hormone replacement therapy can be used safely. It was once thought that using it for five years or less to relieve menopausal symptoms had no risks. But the WHI study seemed to show that was not the case.

There are still a lot of unknowns. Many women now take doses of hormones that are lower than the ones used in the WHI trial. Hormones are also delivered not just through pills, but in other forms, like skin patches. We don't know yet whether these lower concentrations and different forms might decrease the risks.

For now, the FDA recommends that women who take hormone replacement therapy for menopausal symptoms take the lowest effective dose and for the shortest time period to alleviate symptoms.

With all of the contradictory messages, it's hard for a woman to know what to do. There's also a lot of lingering anger about what happened in the wake of the Women's Health Initiative results.

"I lost a lot of faith in my doctors after that," says April Dawson, a 63-year-old Connecticut woman who used hormone replacement therapy for about a year. "And all of the women I know feel the same way.

"In the first place, I didn't like the idea of going on medication when I didn't have any symptoms," Dawson tells WebMD. "But I feel like my doctors ganged up on me and pushed me to take it."

Today, doctors are far more likely to tell each woman that she must make the decision herself, weighing the pros and cons of hormone replacement therapy, considering her symptoms, family history, lifestyle, and risk of disease.

If you take HRT, keep in mind that the absolute risks are low. But you should still regularly check in with your doctor. Ask if there is any new information that might cause you to rethink your decision.

"Hormone therapy is a field that continues to change rapidly," says Shuster. "Treatment has to be more individualized than ever. Women are seeking the one right answer, but for now, we just don't have one."

SOURCES: American College of Obstetricians and Gynecologists web site,"Frequently Asked Questions about Hormone Therapy, "News release: ACOG IssuesState-of-the-Art Guide to Hormone Therapy." Chen, WY et al, Archives ofInternal Medicine, May 8, 2006; vol 166: pp1027-1032. April Dawson,Milford, Conn. Jacques Rossouw, MD, project officer for the Women's HealthInitiative at the National, Heart, Lung and Blood Institute, Bethesda, MD.Salpeter, SR et al, JGIM, July 2004; vol 21: pp 363-366. Salpeter, S,Climacteric 2005; vol 8: pp307-310. Salpeter, SR et al, Diabetes,Obesity and Metabolism, in press. Salpeter, SR et al, Journal ofGeneral Internal Medicine, July 2004; vol 19: pp 791-804. Shelley R.Salpeter, MD, clinical professor of medicine at Stanford University's School ofMedicine. Isaac Schiff, MD, chief of obstetrics and gynecology at MassachusettsGeneral Hospital in Boston; chair of the American College if Obstetricians andGynecologists Task Force on Hormone Therapy. Lynne T. Shuster, MD, director ofthe Women's Health Clinic at the Mayo Clinic in Rochester, MN. Stefanick, ML etal, JAMA, April 12, 2006; vol 295: pp 1647-1657. U.S. Food and DrugAdministration web site, "Questions and Answers for Estrogen and Estrogen withProgestin Therapies for Postmenopausal Women."

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