In an article published in American Journal of Human Genetics on 3 August 2017, an international group of 11 organisations with genetics expertise has issued a joint position statement, setting out 3 key positions on the question of human germline genome editing:

(1)At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy.

(2)Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research.

(3)Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input.

This serendipitously timed statement comes on the heels of Shoukhrat Mitalipov and colleagues at Oregon Health and Science Universitys publication of an article in Nature reporting the successful use of CRISPR/Cas9 in human embryos to correct a mutation in a gene called MYBPC3 that causes a potentially fatal heart condition known as hypertrophic cardiomyopathy. The publication of this article has drawn the attention of the wider mainstream media and reignited the public debate as to the desirability, feasibility and ethics of editing the human genome in an inheritable way.

Gene editing - putting the paper in context

Whilst debates about the ethics of gene editing (both somatic and germline) go back decades, human germline genome editing has never before been realistically possible from a technical standpoint. That has changed with the advent of the CRISPR/Cas9 system, whose efficiency and ease of use has not only opened up the field of gene editing to a far larger number of companies and laboratories than previously, but has brought the editing of specific genes in a human embryo out of the realms of fantasy into reality. The potential for such technology to improve quality of life and prevent suffering caused by debilitating genetically inherited diseases has captured the imagination of many, particularly people living with currently intractable genetic conditions, their friends and family. However, the power of the technology has also conjured up the familiar spectres of playing God, the uncertainty of long term effects on individuals (and what it means to be human itself), marginalisation of the disabled or genetically inferior and the potential for inequality to manifest itself genetically as well as socioeconomically.

Germline cell editing poses significantly more concerning ethical and regulatory issues than somatic cell editing. The latter will only result in uninheritable changes to the genome of a population of cells in the particular individual treated, whilst the former involves genetic changes that will be passed down, for better or worse, to the individuals offspring.

In early 2015, the first study demonstrating that CRISPR/Cas9 could be used to modify genes in early-stage human embryos was published. Although the embryos employed for those experiments were not capable of developing to term, the work clearly demonstrated that genome editing with CRISPR/Cas9 in human embryos can readily be performed. That report stimulated many scientists and organisations to clarify their stance on the use of genome-editing methods. The United Kingdom and Sweden have both approved experiments for editing DNA of a human embryo but not those that involve implanting embryos. In the UK, Human Fertilisation and Embryology Authority (HFEA) has approved an application by developmental biologist Kathy Niakan, at the Francis Crick Institute in London, to use CRISPR/Cas9 in healthy human embryos. Currently, such experiments cannot be done with federal funding in the United States given a congressional prohibition on using taxpayer funds for research that destroys human embryos. Congress has also banned the U.S. Food and Drug Administration from considering a clinical trial of embryo editing. As would be expected, the safety requirements for any human clinical genome-editing application are extremely stringent.

However, earlier this year, US-based National Academy of Sciences (NAS) and the National Academy of Medicine (NAM), published a report that concluded using genome-editing technology, such as CRISPR/Cas9, to make alterations to the germline would be acceptable if the intention was to treat or prevent serious genetic disease or disorders, and the procedure was proven to be safe ( significant and, to an extent, subjective hurdles to be overcome).

The ASHG position paper

The position paper was the product of a working group established by the American Society of Human Genetics (ASHG), including representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counsellors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counsellors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The group, composed of a combination of research and clinical scientists, bioethicists, health services researchers, lawyers and genetic counsellors, worked together to integrate the scientific status of and socio-ethical views towards human germline genome editing.

As part of this process, the working group reviewed and summarised nine existing policy statements on gene editing and embryo research and interventions from national and international bodies, including The International Society for Stem Cell Research (2015) Statement on Human Germline Genome Modification, The Hinxton Group (2015) Statement on Genome Editing Technologies and the statement released following the International Summit on Human Gene Editing (2015) co-hosted by the National Academy of Sciences, National Academy of Medicine, Chinese Academy of Sciences and The Royal Society (UK). It was observed that differences in these policies include the very definition of what constitutes a human embryo or a reproductive cell, the nature of the policy tool adopted to promote the positions outlined, and the oversight/enforcement mechanisms for the policy. However, by and large, the majority of available statements and recommendations restrict applications from attempting to initiate a pregnancy with an embryo or reproductive cell whose germline has been altered. At the same time, many advocate for the continuation of basic research (and even preclinical research in some cases) in the area. One notable exception is the US National Institutes of Health, which refuses to fund the use of any gene-editing technologies in human embryos. Accordingly, due to the lack of public funding in the US, work such as that done by Mitalipovs group must be privately funded.

The working group considered that ethical issues around germline genome editing largely fall into two broad categories those arising from its potential failure and those arising from its success. Failure exposes individuals to a variety of health consequences, both known and unknown, while success could lead to societal concerns about eugenics, social justice and equal access to medical technologies.

The 11 organisations acknowledged numerous ethical issues arising from human germline genome editing, including:

exposing individuals to potentially harmful health consequences, since the magnitude of the potential risks of off-target or unintended consequences are yet to be determined;

the risk that if highly restrictive policies are placed on the conduct and public funding of basic research in the field, this could push research out of the public eye and public interest, underground to private funders or overseas, to organisations and territories where it would be subject to less regulation, transparency and oversight. This could result in research not being subject to ethical and peer oversight, such as ethics board approval, data sharing, peer review and dissemination of research resources;1

the de facto inability of future individuals who are the result of genetic editing, to consent to that editing;

concerns around the boundaries of eugenic use of gene editing technology, which the groups acknowledged could be used to reinforce prejudice and narrow definitions of normalcy in our societies; and

ensuring the gene editing technologies do not worsen existing or create new inequalities within and between societies, noting: Unequal access and cultural differences affecting uptake could create large differences in the relative incidence of a given condition by region, ethnic group, or socioeconomic status. Genetic disease, once a universal common denominator, could instead become an artifact of class, geographic location, and culture. A dangerous consequence of such inequality could be that reduced incidence and reduced sense of shared risk could affect the resources available to individuals and families dealing with genetic conditions.

Having touched on each of these issues, the group then outlined its consensus positions:

1. At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy.

It was noted that there is not yet a high quality evidence base to support the use of germline genome editing, with unknown risk of health consequences and ethical issues still to be explored and resolved by society.

The group observed that two major categories of safety concerns are (i) the effect of unwanted or off-target mutations, and (ii) the potential unintended effects of the desired on-target base changes (edits) being made. It noted that it is reasonable to presume that any human genome-editing therapeutic application will require stringent monitoring of off-target mutation rates, but there remains no consensus on which methods would be optimal for this, or what a desirable maximum off-target mutation rate would be when these techniques are translated clinically. The working-group thus outlined its views on the minimum necessary developments that would be required (at least from a safety perspective) before germline genome editing could be used clinically:

definitions of broadly acceptable methodologies and minimum standards for measuring off-target mutagenesis;

consensus regarding the likely impact of, and maximum acceptable thresholds for, off-target mutations; and

consensus regarding the types of acceptable genome edits with regard to their potential for unintended consequences.

2. Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research.

The group agreed that conducting basic scientific [techniques?] involving editing of human embryos and gametes can be performed ethically via compliance with applicable laws and policies, and that any study involving in vitro genome editing on human embryos and gametes should be conducted under rigorous and independent governance mechanisms, including approval by ethics review boards and meeting any other policy or regulatory requirements. Public funding for such research was seen as important in ensuring that such research is not driven overseas or underground, where it would be subject to less regulation, oversight and transparency.

3. Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input.

Even if the technical data from preclinical research reaches a stage where it supports clinical translation of human germline genome editing, the working group stresses that many more things need to happen before translational research in human germline genome editing is considered. The criteria identified by the group in this position cut across medical, ethical, economic and public participation issues and represent the setting of an appropriately high and comprehensive standard to be met before human germline genome editing may be applied clinically. The group acknowledges the challenges of public engagement with such technical subject matter but encourages new approaches to public engagement and engagement of broader stakeholder groups in the public discussion.

The ethical implications of altering the human germline has been the subject of intense discussion in recent years, with calls for such work to be put on hold until the process of genome editing is better understood. ASHG supports somatic genome editing and preclinical (in vitro human and animal) germline genome research but feels strongly that it is premature to consider human germline genome editing in any translational manner at this time.

The working group concludes that Many scientific, medical, and ethical questions remain around the potential for human germline genome editing. ASHG supports somatic genome editing and preclinical (in vitro human and animal) germline genome research but feels strongly that it is premature to consider human germline genome editing in any translational manner at this time. We encourage ethical and social consideration in tandem with basic science research in the upcoming years.

This appears a reasonable position largely in line with the recommendations from the major national and international groups surveyed by the working group. It balances the need to encourage further basic research and validation with strong awareness of the ethical and societal implications of human germline genome editing, setting a high bar before such technology should be translated to the clinic. No doubt, however, the debate will continue, particularly in respect of public funding for such work. Whether the US will maintain their stance against public funding, in the face of international competition, and potential loss of talent and investment, remains to be seen.

Footnotes

1. In this connection it should be noted that China is a good example of a jurisdiction where there is very strong government investment in biotech, including CRISPR, and less regulatory standards than in the West. This combination of factors seems to be fuelling the pace of research there (many CRISPR firsts have come in China e.g. first CRISPR clinical trial in humans; first CRISPR editing of human embryos), but potentially at the risk of less rigorous, well controlled science being conducted (e.g. the recent retraction of the NgAgo paper).

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Human Germline Genome Editing Genetics bodies weigh in on debate with position paper - JD Supra (press release)

School districts are in a quandary over students who use medical marijuana, with some fearing that any help they offer could land them in jail.

Voters in November agreed to legalize pot for medical purposes but its also a popular recreational drug considered illegal by the federal government. And that has raised a number of questions as districts scramble to put policies in place. Among them:

-- Will local schools store the the drug on school premises or will parents have to come on campus to give it to their child?

-- What forms of the drug will be acceptable on campus? Can students apply cannabis ointments or patches on their skin or bring edible brownies in their lunchboxes?

-- What steps will schools take to prevent the drug from getting into the hands of other students?

Palm Beach County Schools Superintendent Robert Avossa said he plans to talk to School Board members to get a sense of what would best serve community.

We want to show compassion and also use common sense, he said. We may have to deal with it on a case-by-case basis.

Broward County school officials say they are awaiting guidance from the state Department of Education.

However, Lisa Maxwell, who heads the Broward County Principals and Assistants Association, said her group would fight any attempts to make administrators responsible for dispensing or storing the drugs. She said the federal government may disagree with the states decisions to allow minors to access the drugs, and that would put her members in legal peril.

We would vehemently oppose anyone being required to administer something that they could ultimately be criminally prosecuted for doing, she said.

School districts could potentially lose federal funding for school lunches and Title 1 programs for low-income students since the policies run afoul of federal government drug-free workforce policies, warned the Education Commission of the States, which studies education policy.

The expansion of marijuana use policies in the states has largely gone unchecked by federal officials; however, the expansion into schools presents a different set of issues and could meet some federal pushback, the commission wrote in a recent policy paper.

Seth Hyman of Weston is pushing Broward to move ahead on the issue.

His 11-year-old daughter, Rebecca, has a condition that requires her to use a wheelchair and a feeding tube. She also is prone to epileptic seizures.

Taimy Alvarez / Sun Sentinel

Seth Hyman plays with his daughter, Rebecca, 11, has 1P36 Deletion Syndrome, a genetic disorder, who benefits from medical marijuana in their Weston home.

Seth Hyman plays with his daughter, Rebecca, 11, has 1P36 Deletion Syndrome, a genetic disorder, who benefits from medical marijuana in their Weston home. (Taimy Alvarez / Sun Sentinel)

She takes medical marijuana orally three to four times a day, but she cant take it at her school, Manatee Bay Elementary, because the school doesnt have a policy that covered it.

I would like my daughter to have the option to get her medication however the law allows, he said.

Hyman believes school districts are protected due to the state law.

He works for Kelley Kronenberg, a Fort Lauderdale law firm, advising employers on how to comply with the law. He points to a 2013 memo by the U.S. Justice Department saying it was not a priority to enforce federal drug laws for people possessing marijuana for medical purposes. While the memo was from the Obama administration, Hyman said President Trump hasnt seemed concerned about medical marijuana.

Still, he admits there are no guarantees his administration wont try to ban it in schools,

But if that does come to fruition, there will probably be thousands of parents with medically complex kids kicking and screaming asking why they are being denied medicine that has not been proven to kill anyone, Hyman said. People have a right to some sort of improvement in their medical condition.

stravis@sunsentinel.com, 561-243-6637 or Twitter @smtravis

Continued here:

Medical marijuana's legal, but schools fear crackdown if students use it - Sun Sentinel

Some are saying that Sen. John McCains brain cancer, glioblastoma, was the result of long-term cellphone usage. We had a dear friend, Dennis, who died of the same brain cancer, but I doubt that he ever once used a cellphone.

Where is the truth about the dangers of using your cellphone? Answer: Nobody really knows, but there are indications that caution is advised.

What is glioblastoma?

Glia comes from the same word in Greek that means glue. Glia refers to several cell types that are not neurons, but which, since their discovery in 1856, have been commonly thought of as the glue that holds your nervous system together. This is true in a sense, but glial cells do more than that.

Its true that glial cells surround neurons everywhere in your body and hold them in place like glue. They are also rich in blood vessels, and so they provide nutrients and oxygen to your neurons. In addition, glial cells form the myelin sheath that surrounds your neurons, insulating one neuron from another and also getting rid of pathogens and dead neurons.

The -oma ending in medical jargon frequently refers to a type of cancer, where cells begin to grow out of control. Blast refers to cells that are precursors to other cells. That is to say that before a particular glial cell comes to be, it is preceded by an undifferentiated cell called a blast. Blastomas begin in blasts.

In the case of glioblastoma, it usually begins in cells that have the potential to differentiate into the type of glial cell called an astrocyte. There are other types of cancer that begin with astrocytes, all called astrocytomas, but glioblastomas account for over half of them.

Glioblastomas are the most invasive of brain tumors in that they grow very rapidly and spread readily to surrounding tissues, making them difficult to remove surgically. They may contain more than one type of cell, so that treating and killing one type of cancerous cell may leave another type to continue growing.

Incidentally, there is also relatively recent research showing that various dysfunctions in your astrocytes may play a role in psychiatric disorders like autism and schizophrenia.

Its about radiation.

Radiation is all around you. Your voice radiates sound waves. A lighted match radiates heat and light waves. The X-ray machine radiates X-radiation. And more.

All of the atoms and molecules in the universe are constantly moving around, jiggling, bumping into things. Heat is the energy that something has because of this movement, and the faster this happens, the more heat is involved. For example, you see water boil because the molecules are moving around and bumping into each other so fast that the original space isnt big enough to contain them.

Sound waves are waves that physically displace air in certain patterns. You hear because of the pattern of the waves of air that enter your ear; without air, there is no sound. The faster the waves arrive at your ear, their frequency, the higher is the pitch you hear. The greater the top-to-bottom height of the waves, the amplitude, the louder is the sound.

Light is an example of electromagnetic radiation, which doesnt require air and is very different from sound and heat, although EMR may cause heat. Rather, EMR consists of perpendicular waves of electricity and magnetism that always travel at the same speed in a vacuum, the speed of light. EMR also behaves as though it were a string of particles, which are called photons. That is, EMR is both immaterial and material simultaneously.

EMR carries a certain amount of energy that is dependent on the frequency of the waves. Low frequency is low energy, and high frequency is high energy. The spectrum of EMR is conventionally divided into segments from low to high energy called radio waves (RF), microwaves, infrared (IR), visible light, ultraviolet, X-rays and gamma rays. A single gamma photon may have 100,000 times as much energy as a red light photon.

Dangers of EMR

Remember that your cells are chock full of DNA, the material that contains your genes, and genes are the biological computer programs that affect much of whats happening in you. A healthy life is critically dependent on your DNA genetic structure having integrity in itself.

As it happens, with exposure to high-energy EMR, like X-rays and gamma rays, a photon can knock an electron off a DNA molecule, ionize it, which can lead to cancer. At lower frequencies, such as RF and microwaves, there is generally not enough energy to disrupt the DNA in that way; the photons are not ionizing.

However, the lower-energy EMR does affect living tissue by generating heat as you may have experienced through sunburn. And youve probably cooked some food using the heat generated by EMR in a microwave oven.

How can your cellphone hurt you?

EMR is all around you: broadcasting radio and TV, Wi-Fi and Bluetooth, microwave cooking, cordless phones, cellphones and towers, satellite phones, and many more.

The problem with the RF and microwave EMR is that they can cause production of compounds called peroxynitrites in your cells. These are derived chemically from nitric oxide, which is an important contributor to your health under normal circumstances. When overactivated by RF radiation, however, NO is a major player in a complex chemical process that results in peroxynitrite damage to your mitochondria.

Mitochondria are those energy producing factors found in most of your cells, and their health is critical to preventing cancer. The most dense concentration of mitochondria you have is in your brain. So while talking on your cellphone, or cordless phone, you are directly applying RF radiation to a most RF-sensitive area of your body.

It was long thought that genetic mutation was the primary cause of cancer. However, research has shown that while genetic mutation is often causative, its only a secondary cause of cancer. The primary cause lies with your mitochondria. That is, mitochondrial damage happens first, and then triggers genetic mutations that may lead to cancer. For more information, see my June 17, 2016, column, The prevention and treatment of cancer.

Research: inconclusive, but suggestive

There has been research into the effects of RF radiation on human health, and especially cancer. Much of the research has been limited and of poor quality, and so its difficult to conclude definitely that cellphone usage will cause cancer.

While not conclusive, however, there is enough credible evidence suggesting a link between cellphones and cancer that the International Agency for Research on Cancer says that RF radiation is a possible human carcinogen. There is a growing body of evidence supporting that link, and urging caution.

How to be cautious

It seems extremely unlikely that we will stop using cell or cordless phones in the foreseeable future. There are, however, several things you can do to minimize your risk of disease from RF radiation.

First, if you must hold the phone to your head, keep your conversations short.

Better yet is to keep the phone away from your body by using its speaker phone feature or by sending text messages instead of having a conversation.

Limit the use of your phone when the reception is weak, three bars or less. The reason is that a weak signal forces your phone to increase the power of its RF signal in order to communicate with the cell tower.

Carry your phone away from your body in a purse or backpack if you can. Separation even as little as an inch between you and the phone antenna can make a big difference in the amount of RF radiation youre receiving.

Its a question mark.

Did McCains cellphone usage cause his brain cancer? We cant know that, and we cant know if your pattern of cellphone and cordless phone usage will damage your health. We do know that there are real risks associated with the use of these phones, and its a simple matter to minimize them.

Bob Keller maintains a holistic pain management practice in Newburyport. His book, Making Sense of Medicine: Medical Matters Made Simple, is available locally or online. He can be reached at 978-465-5111 or bob@myokineast.com.

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Making Sense of Medicine: Is your cellphone killing you? - The Daily News of Newburyport