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How Flesh-Eating Strep Bacteria Evolved into an Epidemic

April 15, 2014

(Wired) – Bacteria aren’t kind enough to leave behind a fossil record (save for cyanobacteria), but they’re evolving fast. Really fast. Their short life cycles mean that generations come rapid-fire, adapting through natural selection into the monster pathogens that are currently shrugging off our finest antibiotics. It’s all the more troubling when we’re dealing with the flesh-eating variety. A new study, published today in the Proceedings of the National Academy of Sciences, details the evolution of one such bacteria, group A Streptococcus. By charting its evolution, scientists hope to gain invaluable insights into tackling subsequent generations of these menaces, and to begin to better understand the very nature of epidemics.

Consumers Considering Different Health Plans Find Little Info about Abortion Coverage

April 15, 2014

(Washington Post) – When it comes to coverage of abortion services in plans sold on the health insurance marketplaces, opponents and supporters of abortion rights are in agreement on one thing: Coverage details need to be clearer. A recent analysis by the Guttmacher Institute, a reproductive-health research and policy organization that supports abortion rights, found that people in some states would be hard-pressed to find any information about whether the plans they were interested in covered abortion services.

Could Silly Putty Help Treat Neurological Disorders?

April 15, 2014

(Medical News Today) – It seems unlikely that Silly Putty – a children’s moulding toy – could prove useful in the medical world. But new research from the University of Michigan suggests that a key ingredient used in Silly Putty can turn embryonic stem cells into working spinal cord cells more efficiently. The research team, including Jianping Fu, professor of mechanical engineering at the University of Michigan (U-M), says their findings may lead to new treatments for neurological disorders, such as amyotrophic lateral sclerosis (Lou Gehrig’s disease), Huntington’s disease or Alzheimer’s disease.

Fertility Tourism: Couples Desperate for a Baby Heading Overseas

April 15, 2014

(The New Zealand Herald) – As a result of the 2002 law, lower costs, increasing medical infrastructure and the availability of surrogates, the country has emerged as a hotspot for this type of fertility tourism. International surrogacy, also legal in the United States, Thailand, the Ukraine and at least one state in Mexico, is a growing trend for couples and singles, both gay and straight, seeking ways to overcome the hurdles biological, technological, financial, and legal of having children.

Genetics Leader Reflects on 50th Anniversary of Discovery of Genetic Code

April 15, 2014

(Baylor College of Medicine) – In 1959, postdoctoral associate Dr. Thomas Caskey, participated in the Nobel Prize winning work of Dr. Marshall Nirenberg that helped unravel the genetic code of life. It was not just a “one-trick pony,” Caskey reflected. Nirenberg won the Nobel Prize for this work which unveiled the set of rules by which information encoded without genetic material  (DNA or mRNA sequences) is translated into proteins by living cells.

Gene Editing Technology

April 14, 2014

What Is Gene Editing?

People sometimes express concerns over gene therapy, which is genetic engineering for therapeutic purposes, but what they are really concerned about is gene editing. Genetic engineering is a relatively straightforward procedure in the laboratory, and is the basis of the field of synthetic biology. Genes are made of DNA, and scientists are able to make any DNA sequence they want using a computer and laboratory equipment. Technically speaking, this is genetic engineering. While making a DNA sequence in a lab is relatively simple, inserting it into a cell and replacing the unwanted DNA, is an entirely different technique. The insertion or deletion of DNA may be more accurately described as gene editing.

Gene editing has been notoriously difficult to do. The best techniques have involved designing proteins that take a long time to make and are difficult to work with in the lab. Additionally, these gene editing techniques can only edit one segment of DNA at a time. This makes it difficult for scientists to study disease models (usually in mice) involving more than one genetic marker. Recently, however, several studies have touted a new gene editing technique called CRISPR (clustered regularly interspaced short palindromic repeats) that has already shown in animal models that it is easier to use and can change more than one portion of DNA at a time.

Gene therapy received a bad reputation in 1999 when 18-year-old Jesse Gelsinger, a clinical trial participant, died from a poor reaction to a technique involving the insertion of genetic material to potentially cure a rare genetic disease. This case was controversial for many reasons, including financial conflict-of-interest issues and proper informed consent. As a result of this case, as well as other cases that came to light upon investigation, gene therapy research and clinical trials decreased dramatically for a number of years.  However, a recent Wired article entitled “The Fall and Rise of Gene Therapy” optimistically reported that improvements in gene insertion into cells have led to a resurgence of the field.

(It is notable that the Wired article was criticized for leaving out pertinent historical facts regarding the Gelsinger case and the ethical controversies surrounding the gene therapy field at the time.  An informative response to the article can be found here.

Finding the right virus to target cells and insert DNA segments into those cells is only part of the story.

New Tools for Gene Editing

In order for scientists to determine what a gene actually does and whether it is the cause of a disease, they will do animal studies in which they remove the gene and see what changes occur in the animal, such as looking for disease symptoms. This is usually done in mouse models, and it usually takes many years to adequately remove or “silence” a gene. Using the CRISPR method scientists are now able to remove a gene in a matter of weeks. Additionally, with these techniques they are able to guide where the DNA is inserted, rather than just inserting it randomly into the cell.

Prior methods to delete and insert DNA were more cumbersome. In 1996, scientists developed a technique called zinc-finger nuclease (ZFN) in which scientists made a protein nuclease in the lab that targeted a specific portion of DNA that would then cut the DNA. But, scientists needed to make a new nuclease every time they wanted to investigate a different portion of DNA. This process was expensive and time consuming. It also was only good for one genetic modification at a time, making it difficult to investigate diseases that have more than one genetic marker.

In 2010, scientists developed a different nuclease technique that was easier to work with than ZFNs called TALEN (transcription activator-like effector nucleases). These nucleases are easier to design for a specific DNA target, but their large size presented practical problems in the lab.

Finally, in January 2013, scientists demonstrated that a method that bacteria use to inoculate themselves from viruses can also be used as a gene editing technique in humans. (See here for the research article.) This latest method is CRISPR. It requires a nuclease called CAS9 and a piece of RNA (similar to DNA) that scientists can make in the lab. Unlike prior methods for gene editing, the same nuclease can be used to edit any DNA target. The RNA segment tells the CRISPR/CAS9 system where to cut the DNA. Not only can it remove DNA, but it can also guide the cell’s DNA repair mechanisms to the precise location for inserting the edited DNA. ZFNs and TALENs also use the cell’s repair mechanisms to guide DNA, but CRISPR is much easier to work with and, importantly, much faster. Using CRISPR, several genes can be deleted and others inserted in mouse models in a matter of weeks rather than years. Several research groups and start-up companies are now studying CRISPR and refining the technique.

Use in Stem Cell Therapy

One way that scientists are hoping to use CRISPR is in stem cell therapy. For example, Susan Young in MIT Technology Review reports that Gang Boa’s group is looking into ways to overcome the immune response when a patient receives a donor’s stem cells. They are testing whether they can remove bone marrow stem cells from people with sickle cell disease, use CRISPR to edit out the offending gene sequence that causes sickle cell, and then re-insert the edited stem cells back into the patient. This is just one of several possibilities using CRISPR techniques. According to Young, “In little more than a year, CRISPR has begun reinventing genetic research.”

Bioethics Issues

Many of the same concerns that have been mentioned on this site in regards to genetic engineering apply to gene therapy using CRISPR (See “Mighty Mitochondria and Assisted Reproductive Technology” and “Genetics in the News”. Not every trait or disease has a purely genetic basis. Also, if someone has a gene for a particular disease, in many cases, that only means he or she may get the disease. Pre-emptively removing a gene that has not been fully characterized may lead to unforeseen adverse effects. Sometimes genes have both “good” and “bad” effects. Additionally, sometimes the same gene may be recruited for different purposes. We, therefore, need to exercise caution when moving into areas in which our knowledge is still incomplete.

The most pressing bioethics issue is that of safety. CRISPR will not be in the clinic for a long time because, just as with its predecessors, ZFNs and TALENS, it sometimes cuts the DNA in the wrong spot.  Off-target cutting can be lethal to cells. Much of the current research on CRISPR is finding ways to ensure accurate editing. Even being off by one nucleotide can wreak havoc on an organism, so until gene editing becomes more accurate, it will continue to be limited to studying model diseases or possibly for stem cell research.

Another ethical issued is raised by Harvard scientist George Church in Young’s MIT Technology Review article. He points out that once gene editing is able to cure diseases, “some scientists will be tempted to use it to engineer embryos during in vitro fertilization. Researchers have already shown that genome editing can rewrite DNA sequences in rat and mouse embryos, and in late January, researchers in China reported that they had created genetically modified monkeys using CRISPR. With such techniques, a person’s genome might be edited before birth—or, if changes were made to the eggs or sperm-­producing cells of a prospective parent, even before conception.”

This brings up issues of autonomy and human dignity. Gene editing techniques could/might allow parents to make genetic decisions for their children. Furthermore, as we have seen with the American eugenics movement, fear of mental illness or other culturally driven preferences may lead some parents to decide to have their embryo’s genome edited without fully understanding the complex genetic basis, if there is a genetic basis, behind these traits. This delves into even more fundamental questions on the role that genetics plays in determining our traits.

The human genome is complex, and scientists are still learning the nuances of the genetic code and how genes are expressed. While using CRISPR technology to study disease in animal models seems to have a practical value, the consequences of editing certain genes in the human genome are still largely unknown. There are a small number of genetic diseases that are directly due to a particular error in the genetic code, but many diseases are due to a complexity of factors in which it’s unclear whether genetic editing would do more harm than good.

For an academic review article on ZFNs, TALENs, and CRISPR, see Trends in Biotechnology, Volume 31, Issue 7, 397-405, 09 May 2013. Subscription required.

IVF Patient Pregnant with Another Couple’s Twins in Embryo Mix-Up

April 14, 2014

(News.com.au) – A WOMAN who underwent fertility treatment at a clinic in Rome became pregnant with the twins of another couple after their embryos were mixed up. Italy’s health ministry says it’s launching an investigation into the error, which was only discovered when the woman was three-months-pregnant.

Finding the Switch: Researchers Create Roadmap for Gene Expression

April 14, 2014

(Medical Xpress) – In a new study, researchers from North Carolina State University, UNC-Chapel Hill and other institutions have taken the first steps toward creating a roadmap that may help scientists narrow down the genetic cause of numerous diseases. Their work also sheds new light on how heredity and environment can affect gene expression.

Payment Bid to Boost IVF Cycle

April 14, 2014

(Sydney Morning Herald) – Women who donate their eggs so others can have children would be paid for their trouble, under changes to the IVF code of ethics being considered by Australia’s chief medical advisory and research authority. As part of its review of the ethical guidelines for the practice of assisted reproductive technology in Australia, the National Health and Medical Research Council has sought public comment on whether women should be ”compensated for the reproductive effort and risks associated with donating their eggs”.

Pure Samples of Individual Amino Acids Successfully Identified through Recognizing Tunneling

April 14, 2014

(A to Z Nanotechnology) – Some three billion base pairs make up the human genome – the floorplan of life. In 2003, the Human Genome Project announced the successful decryption of this code, a tour de force that continues to supply a stream of insights relevant to human health and disease. Nevertheless, the primary actors in virtually all life processes are the proteins coded for by DNA sequences known as genes.

Will Synthetic Biology Evolve into the Next Hot Field?

April 14, 2014

(Yahoo News) – Synthetic biology grew from a very old human desire to engineer living systems and make them do useful things for us. As genetic engineering of the 1970s has evolved into synthetic biology today, the technologies and economics for sequencing (reading) and synthesizing (writing) DNA have become optimized for large-scale DNA processing. This allows synthetic biologists to design and modify the genetics of living systems so that they produce a wide variety of materials for us that don’t occur in nature, such as drugs, biofuels, flavors, fragrances and more.

Brain Cell Discovery Could Open Doors to Targeted Cancer Therapies

April 14, 2014

(Eurekalert) – Fresh insights into the processes that control brain cell production could pave the way for treatments for brain cancer and other brain-related disorders. Scientists have gained new understanding of the role played by a key molecule that controls how and when nerve and brain cells are formed – a process that allows the brain to develop and keeps it healthy. Their findings could help explain what happens when cell production goes out of control, which is a fundamental characteristic of many diseases including cancer.

Phase 1 Trial for ALS Results of Novel Stem-Cell Therapy Presented by Neuralstem Representative

April 14, 2014

(Bio News Texas) – Neuralstem, a company that specializes in producing commercial quantities of neural stem cells of the brain and spinal cord, publicly presented the findings of their Phase 1 clinical trial involving amyotrophic lateral sclerosis (ALS) at the Keystone Symposia “Engineering Cell Fate and Function,” occurring April 6-11 in Olympic Valley, California. Results were published in Annals of Neurology in mid-March, but principal investigator Eva Feldman, PhD, MD, discussed the results of Neuralstem’s NSI-566 stem cell trial in ALS during a workshop on “Clinical Progress for Stem Cell Therapies” at the symposia.

Stem Cells Seen as Promising in Lupus

April 14, 2014

(Med Page Today) – Mesenchymal stem cell transplantation is showing promise as a treatment for refractory systemic lupus erythematosus, researchers have reported. In a multicenter study conducted in China that included 40 patients who had persistent disease despite aggressive treatment with cyclophosphamide, mycophenolate mofetil, leflunomide, and/or high-dose steroids, 60% of those given umbilical cord mesenchymal stem cells had a major or partial clinical response during a year of follow-up, according to Lingyun Sun, MD, of Nanjing University Medical School, and colleagues.

Former NIH Stem-Cell Chief Joins New York Foundation

April 14, 2014

(Nature) – Stem-cell biologist Mahendra Rao, who resigned last week as director of the Center for Regenerative Medicine (CRM) at the US National Institutes of Health (NIH), has a new job. On 9 April, he was appointed vice-president for regenerative medicine at the New York Stem Cell Foundation (NYSCF), a non-profit organization that funds embryonic stem-cell research.

Harvard Investigation Leads to ‘Expression of Concern’ on Brigham-Led Stem Cell Research

April 14, 2014

(Boston.com) – Two days after a heart research paper was retracted, questions have been raised about a stem cell study overseen by the same prominent Brigham and Women’s Hospital cardiovascular researcher. In an “expression of concern” posted online Thursday night, editors of the British medical journal The Lancet said Harvard Medical School had notified them of an ongoing investigation examining the “integrity of certain data” used in two sets of images of cells in a 2011 paper overseen by Dr. Piero Anversa at the Brigham.

Dubai Rolling Out Red Carpet for Medical Tourism Patients

April 14, 2014

(Medical Tourism Magazine) – The Dubai Health Authority has its eyes set on attracting 500,000 medical tourism patients a year and plans to build 22 hospitals, boosting the national economy by up to Dh2.6 billion by 2020. Designs aimed at making Dubai a major center for medical tourism in time for when the United Arab Emirates land territory hosts World Expo 2020 include the hiring of thousands of healthcare staff and new visas.

ASU Leads New National Research Network to Study Impacts of Nanomaterials

April 14, 2014

(Phys.org) – Arizona State University researchers will lead a multi-university project to aid industry in understanding and predicting the potential health and environmental risks from nanomaterials.  Nanoparticles, which are approximately 1 to 100 nanometers in size, are used in an increasing number of consumer products to provide texture, resiliency and in some cases antibacterial protection.

Event: MedStar Washington Hospital Center Third Annual Regional Clinical Ethics Symposium

April 14, 2014

MedStar Washington Hospital Center for Ethics
3rd Annual Regional Clinical Ethics Symposium
April 21, 2014
Washington, D.C.

See here for more information.

A New Edition of Health Policy and Planning is Available

April 11, 2014

Health Policy and Planning (Volume 29, No. 2, March 2014) is now available online by subscription only.

Articles include:

  • “Impact of user fees on maternal health service utilization and related health outcomes: a systematic review” by Susie Dzakpasu, Timothy Powell-Jackson, and Oona M.R. Campbell
  • “Estimates of performance in the rate of decline of under-five mortality for 113 low- and middle-income countries, 1970–2010” by Stéphane Verguet and Dean T. Jamison
  • “Financial protection in health in Turkey: the effects of the Health Transformation Programme” by Mahmut S Yardim, Nesrin Cilingiroglu, and Nazan Yardim
  • “Health reform and out-of-pocket payments: lessons from China” by Lufa Zhang and Nan Liu
  • “Through the back door: nurse migration to the UK from Malawi and Nepal, a policy critique” by Radha Adhikari and Astrida Grigulis