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Posts Tagged ‘bioethics

Science Policy Around the Web – June 7th, 2019

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By: Mary Weston, Ph.D.

Source: Pixabay

Pfizer had clues its blockbuster drug could prevent Alzheimer’s. Why didn’t it tell the world?

Last Tuesday, the Washington Post reported that the biopharmaceutical company Pfizer had hints that their rheumatoid arthritis drug Enbrel might reduce the risk of Alzheimer’s disease, but chose not to report these findings to the public.

In 2015, after analyzing hundreds of thousands of insurance claims, a team of Pfizer researchers observed that their anti-inflammatory drug Enbrel might also decrease the risk for Alzheimer’s by 64%. They recommended that the company conduct a costly clinical trial to prove the link but, after several years of internal debate, the company decided not to pursue the lead.  The question remains: why did Pfizer not release these findings to the scientific community?

Pfizer claims they did not pursue the research due to scientific considerations – they argue that since Enbrel cannot cross the blood-brain barrier and directly reach brain tissue, it is unlikely to prevent the debilitating neurodegenerative disease. Further, Pfizer claimed that they did not to report the research because the statistical findings did meet “rigorous scientific standards” and were concerned about misleading researchers down a false path. However, Pfizer is also losing its patent protection on Enbrel soon, meaning that generics will become available and the drug will be much less profitable, reducing any financial incentive for further research or clinical trials (likely to cost around $80 million).

Some in the scientific community are questioning Pfizer’s justification. Keenan Walker, an assistant professor of medicine at Johns Hopkins, argues that the scientific community benefits when the data is available, stating that ““[w]hether it was positive data or negative data, it gives us more information to make better informed decisions.’’

Several scientists argue that Pfizer’s results should be release because they could provide clues to combating the disease and slowing cognitive decline in its earliest stages. Specifically, recent research is hinting that inflammation may promote Alzheimer’s disease. Further, neurodegenerative research is notoriously challenging and there are no major drugs that treat Alzheimer’s. Even several recent phase 3 clinical trials have been halted because the drugs were not effective. Due to a lack of progress in the field, a couple large pharmaceutical companies, including Pfizer, have just closed their neurology-related research programs.

 (Christopher Rowland, Washington Post)

Trump administration halts fetal-tissue research by government scientists

The Trump administration has announced that government scientists will stop using human fetal tissue for research and is placing new limitations on researchers in academic settings who use federal funding from the NIH.

It is not entirely known how many research projects will be affected by the new regulations. Government scientists will be allowed to continue their current work, but are prohibited from acquiring new tissue samples. Current extramural research at universities and privately funded work can continue but any new grant proposals or renewals of existing projects must be approved by an ethics advisory board that will be formed.

In addition to halting government fetal tissue research, the administration has decided to cancel an ongoing HIV research contract with the University of California San Francisco, effectively ending a 30-year partnership. The project involves using fetal tissue to develop mouse models with human-like immune systems to develop new HIV therapies.

Use of fetal tissue is essential to for studying certain human biological processes, such as kidney development. Often biomedical research uses mice as substitutes of people, but in this case, murine kidney development is too different from their human counterparts to be of use. Some researchers fear that these new restrictions will set back certain research for years to come. Important areas of research that depend on using fetal tissue including HIV, neurodegeneration, human organ growth and regeneration, Zika (determining how/why the virus affects developing fetuses so severely), and certain types of vaccine development.

POLITICO reports that this decision was made after much debate between the White and the Department of Health and Human Services (HHS), which wanted a less restrictive policy. In a statement released Wednesday, HHS said that “promoting the dignity of human life from conception to natural death is one of the very top priorities of President Trump’s administration.” HHS is now reviewing whether sufficient alternatives to human fetal tissue exist and will be supporting the development and validation of these models. However, good alternatives for certain fetal tissue research are elusive and many scientists say that the tissue is essential for some fields.

 (Sara Reardon, Nature)

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June 7, 2019 at 6:11 pm

Science Policy Around the Web – April 6, 2018

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By: Sarah L. Hawes, PhD

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source: pixabay

Biomedical Research

Mitochondrial Replacement moratorium – are we over-regulating cures?

You may recall learning in grade-school science about the ‘mighty’ mitochondria which function as cellular power-plants, translating energy from your food into ATP to fuel subcellular processes. Failure in this fundamental process results in devastating mitochondrial diseases. Power-hungry tissues of the body – brain, heart, lungs, muscles – are hard hit by mitochondrial dysfunction, leading to degradation of heart, liver, kidney, gastrointestinal, respiratory and brain function. Perhaps you also recall learning that your mitochondrial DNA is a very small fraction of your total DNA, and is inherited solely from your mother? This feature has made it possible for researchers to develop mitochondrial replacement (MR) therapy which can be targeted to the egg prior to fertilization. In this procedure, donated mitochondria replace mutation-bearing mitochondria within unfertilized eggs, allowing women who carry aberrant mitochondrial DNA to give birth to genetically related, healthy children.

Unfortunately, a 2016 moratorium on U.S.-based research in which a human embryo is intentionally created or modified currently prohibits clinical MR therapy despite modification taking place prior to fertilization. Nonetheless, replacing mutation-bearing mitochondria with donated genetic material falls under a broad category of genetic modification prohibited by the moratorium – which has no named authors, and was passed without major congressional or public discussion.

A recent commentary in Obstetrics & Gynecology calling for this moratorium lift was authored by Professors Eli Adashi at Brown University’s Warren Alpert Medical School, and Glenn Cohen at Harvard Law School. Adashi points out the high number of children born in the U.S. annually with mitochondrial disease, and states “…this issue is not about the sanctity of life. There is an inherent hypocrisy in holding this procedure hostage at the expense of 1,000 children each year who are doomed to die a painful death.”

Adashi and Cohen detail a comprehensive process to move forward with reevaluating the moratorium, and laying the groundwork for policy enabling MR therapy in the U.S. These processes would engage the public, medical professionals, patient advocacy groups, the U.S. Food and Drug Administration and Congress. Authors describe a careful 15-year process of policy development in the U.K. ending in 2015 with Parliament approving MR under stringent regulatory oversight and within a single licensed clinic. They also note that, without FDA oversight and approval at home, American families seeking to safeguard their children against mitochondrial disease will seek care abroad given that successful MR therapy has now taken place in both the U.K. and Mexico.

(Gillian Kiley, News from Brown)

The Opioid Crisis

Provisions for legal medical cannabis are associated with reduced opioid use

Last year, the U.S. Department of Health and Human Services declared a public health emergency due to the more than 42,000 deaths from opioid overdose in 2016, with more than 40% of these deaths resulting from prescription medications. Two studies published this week in the Journal of the American Medical Association, Internal Medicine examined the number of opioid prescriptions filled in a recent five-year period, and related this number to coincident medical marijuana laws.

Co-author Bradford from one study explains that “Some of the states we analyzed had medical cannabis laws throughout the five-year study period, some never had medical cannabis, and some enacted medical cannabis laws during those five years,” enabling researchers to ascertain “what happens to physician behavior in terms of their opiate prescribing if and when medical cannabis becomes available.”

Bradfords’s team found that availability of legal medical marijuana via dispensaries was associated with a significant decrease in opiate use, amounting to about 14% fewer annual opiate prescriptions relative to states without legal access. Clearly these findings are correlative, however researchers included a useful control:  the examination of prescription rates for non-opioid drugs such as flu medicine and blood thinners – none of which might be replaced by medical marijuana. The study found no relationship between these prescriptions and marijuana laws. These results suggest that availability of marijuana as an alternative pain treatment alleviates public use of prescription painkillers.

A separate but similar study reports a more modest 6% reduction in the rate of opioid prescription writing coincident with medical marijuana laws. This figure includes states with a broader range of legal access to marijuana, regardless of whether dispensaries exist. Researchers in this group investigated fiscal impact as well:  medical and adult-use laws were associated with a 9.78% reduction in Medicaid spending on opiates, and 8.36% reduction in Medicaid spending on non-opiate pain medications.

There are clear caveats to medical marijuana usage. Effects of cannabis are inadequately understood and require further study. Proper dosage has yet to be clearly defined for this drug.

“Regardless, our findings suggest quite clearly that medical cannabis could be one useful tool in the policy arsenal that can be used to diminish the harm of prescription opioids, and that’s worthy of serious consideration,” said Bradford. Such policy may find broad public backing. In fact, a recent poll by University of Michigan Medical school indicates roughly 80% of persons aged 50-80 (a prime demographic for pain medication) support allowing medical marijuana if recommended by a physician. Given the opioid crisis and public reliance on physician actions (recommendations, prescription-writing), it would be prudent to focus on developing basic and clinical research and policy geared at defining and permitting safe use of opioid alternatives – including marijuana.

(Kate Sheridan, Stat News)

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April 9, 2018 at 11:31 am

Science Policy Around the Web – June 27, 2017

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By: Sarah Hawes, PhD

Source: pixabay

Influenza

An Arms Race with Nature

H7N9, a new bird flu emerging in China, has infected roughly 1,500 people and killed 40% of them. The virus is contracted directly from infected birds but is not yet easily transmissible between humans, however researchers at The Scripps Research Institute have evidence H7N9 could potentially become transmissible between humans fairly easily. They examined a fragment of the virus that interacts with receptors on animal cells to gain entrance, and identified three minor mutations that could cause the fragment to shift from preferentially entering avian cells to preferentially entering human cells. If these mutations were to occur, it could rapidly result in a pandemic.

Tests in a viral fragment do not prove functionality in the intact virus; that would require mutating H7N9 itself. A 2014 moratorium on mutating three types of viruses (SARS, MERS, influenza) to more dangerous forms is expected to lift when the Department of Health and Human Services finishes current work drafting a new policy establishing reviews designed to assess benefit/risk ratios before funding research.

The subject is divisive, even among scientists in the field. Stanford researcher David Relman says he would support efforts to test mutations in a weakened strain of flu, but not in the H7N9 virus.  Bioterrorism expert Thomas Inglesby opposes increasing the contagious lethality of a virus, and opposes publishing such procedures due to concern that less benevolent actors would be enabled to replicate the process. NIH funded researcher, Ron Fouchier in the Netherlands, whose alteration of H5N1 to become highly contagious between ferrets (the animal model for humans) in 2011 influenced the moratorium, believes examining dangerous virus mutations in a controlled lab environment is important to identify potential pandemic viruses.

Many of these topics were discussed at the recent Immunology and Evolution of Influenza Symposium, and are sure to be a hot topic at the July 16 – 19 Centers of Excellence for Influenza Research and Surveillance meeting. With policy guidance needed on benefit/risk, potentially safer models, security, and publication limitations, the new HHS policy will be critical. (Nell Greenfieldboyce, NPR)

Conservation

Modeling with Dough – Pick your Species

The Supreme Court found the Endangered Species Act was “intended to halt and reverse the trend toward species extinction—whatever the cost.” Today, in light of the cost, conservation policy makers are being invited to triage species extinctions. Fish and Wildlife Service representatives recently met with ecologist Dr. Leah Gerber to discuss her proposed use of an algorithm guiding conservation funding.

A self-proclaimed environmentalist, Gerber says her model suggests that defunding “costly failures,” including the spotted owl, golden-cheeked warbler and gopher tortoise, could help save about 180 other species. Gerber says policy makers may opt to continue to support species that her algorithm rejects, as was done for the koala in Australia where algorithm triage has been used. In this case, a popularity contest may determine who lives and who goes extinct.

Details of the algorithm are not explicit, but Dr. Gerber’s recent publication in PNAS is a straightforward return-on-investment calculation analyzing the mathematical relationship between funds requested, spent, and species success or decline.  Gerber finds “the cost–success curve is convex; funding surpluses were common for the species least likely and most likely to recover” so it’s not simply ‘money in – species out’. Other factors – endemism, keystone status, level of species risk – are also important, though Gerber acknowledges they are not currently included.

While proponents call use of the equation “doing the best you can with what you have,” lack of data on its predictive validity make it a frightening policy tool governing something as permanent as species extinction. What if region affects costs, population growth is slower in species reaching sexual maturity later, a break-through in understanding one species’ requirements is just around the corner or we haven’t yet discovered the significance of the niche occupied by another species? What if business or political interests conflict with a species’ needs? What if the algorithm developer seeks intellectual property legal status, as is happening now with a proprietary algorithm used in parole and sentencing situations? Algorithms impacting public policy should be vetted by multiple experts in germane disciplines, validated, and kept publicly accessible for healthy scrutiny. (Sharon Bernstein, Reuters)

 

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June 27, 2017 at 11:42 am

Science Policy Around the Web – June 10, 2017

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By: Allison Dennis, BS

Source: pixabay

Animal Testing

Lack of Clarity Puts Chemical Safety and Animal Welfare at Odds

In the lineup of American stereotypes, the health-nut who cares about the chemicals in his shampoo is often the same person who cares if that shampoo was tested on animals or not. However, a bill signed June 22, 2016, known as the Frank R. Lautenberg Chemical Safety for the 21st Century Act, may be placing those two views at odds. The bill requires the U.S. Environmental Protection Agency (EPA) to implement a risk-based process to evaluate the safety of chemical substances currently being used in the marketplace and approve the use of new chemicals before their introduction. The bill was passed with bipartisan support and offered EPA the new-found power to fully regulate the use of well-known carcinogens like asbestos.

Yet the pathway forward for the EPA is daunting. More than 62,000 substances find their way into and onto our bodies through the products we use and our environment. While many of these substances have become associated with disease over time, how can the EPA certify the risks associated with different exposures to varying amounts of each substance on such an extensive list? The Act itself suggested that once the EPA has evaluated the existing information on the 62,000 substances currently in use, it spend the next twelve months triaging chemicals according to their potential risk. Next, the highest priority chemicals will be evaluated on a three-year deadline to develop knowledge of their toxicity and guidelines for their regulation. Ultimately, by clearly cataloging the risk of common chemicals the Frank R. Lautenberg Chemical Safety for the 21st Century Act promises to greatly reduce the amount of animal testing needed in the long-term.

In the meantime, however, the companies that use to-be-regulated substances in their products may be inclined to undertake independent toxicity testing, collecting enough data to guarantee that their favorite substances meet the low-risk criteria and avoid a drawn-out evaluation. Defining toxicity requires careful experimentation, which can sometimes be carried out in human cells outside of the body, but often require evaluation in animals. Animal rights groups like the Human Society find concern with the lack of transparency in the pre-prioritization process. They fear the eagerness of companies to provide data without any clear guidelines about how that data will be evaluated or what substances will require extensive evaluation could result in extensive and unnecessary animal testing. Further they suggested that the EPA require any new pre-approval data obtained by companies to be collected using non-animal methods. (Maggie Koerth-Baker, FiveThirtyEight)

CRISPR

Small Study may Reveal Big Concerns over CRISPR-Based Therapy

A one-page letter published in Nature Methods last week reports unexpectedly high levels of unintended changes to the genomes of mice that underwent a CRISPR-based therapy. Since it’s renaissance as a therapeutic tool in 2012, CRISPR has occupied the imaginations of scientists, doctors, patients, investors, and ethicists. CRISPR technology provides a relatively straight-forward and reproducible means to gene editing on the cellular level, but its applications to create heritable mutations in the human germ line is on hold until more is understood about the long-term effects such treatments would have.

The original study sought to explore potential long-term effects of germline manipulation by CRISPR in a mouse model. Guide RNA along with the Cas9 enzyme were injected into mouse zygotes, which introduced a correction in a mutation in the rd1 gene of otherwise blind mice. Initiating this change before the first cell division enabled this corrected mutation to be inherited by all cells arising in the developing mouse, consequently restoring the ability for the eyes to develop normally. In a follow-up experiment described in their one page letter, the researchers looked for mutations in the genomic DNA of two CRISPR-treated adult mice compared with a control mouse, revealing over 2,000 unintended mutations following CRISPR treatments. None of these mutations appeared to affect the mice, suggesting that deep genomic sequencing may be required to reveal unanticipated changes in an outwardly healthy mouse. Further, the nature of these unintended mutations offered few clues explaining how they might have occurred.

This result stands in contrast with other reports quantifying the extent of these unintended changes, which found CRISPR to be highly specific. While the CRISPR-Cas9 system has been observed to sometimes alter off-target regions of the genome, this activity can usually be curbed through the careful design and evaluation of the guide RNA. The limitations of this small study have been discussed extensively since its publication. However, the findings have sparked the need for further investigation into the long-term-whole-animal effects of germline-editing by CRISPR. As human germline-editing creeps closer to reality, the FDA will be tasked with developing an entirely new means of evaluating the safety of such technologies (Megan Molteni, Wired)

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June 10, 2017 at 11:33 am

How Science Policy Affects Pandemic Pathogen Research

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By: Samuel Porter, PhD

         In 2012, a pair of studies were published in Nature and Science weeks apart igniting one the biggest national debates about science in recent memory. These studies demonstrated that a few mutations in the highly pathogenic H5N1 strain of influenza virus (colloquially known as “bird flu”) could enable it to be transmitted through the air to mammals. At the heart of controversy was the question of whether scientists should be creating more virulent and/or pathogenic strains of deadly viruses in the lab. This controversial research is known as “gain of function” studies.

Critics claimed that the research was too dangerous that the risk of an accidental or deliberate release of these lab strains was far greater than the scientific and public health benefits. In an attempt to respond to the growing concern over their work, the community of researchers working with these pathogens voluntarily agreed to suspend this gain of function research for 60 days to discuss new policies on conducting the research safely.

But that was not enough to satisfy critics of the research, who continued to lobby the Obama administration to take official action. On October 17, 2014 the White House Office of Science and Technology Policy (OSTP), abruptly announced a pause on all U.S. Government funding of gain of function research on influenza, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS) coronavirus until the National Science Advisory Board for Biosecurity (NSABB) could make recommendations for policy regulating the research going forward. The NSABB was formed in 2005 (in the wake of the anthrax attacks in 2001), and is composed of scientists from universities around the nation, and administrators from 14 separate agencies in the federal government. The board reports to the Secretary for Health and Human Services (HHS) and is tasked primarily with recommending policies to the relevant government entities on preventing published research in the biological sciences from negatively impacting national security and public health.

The move drew harsh criticism from researchers in the field, many of whom thought that it was too broad. They claimed it would jeopardize their ability to predict, detect, and respond to potentially emerging pandemics. In the private sector, several companies said that the order would prevent them from working on new antiviral drugs and vaccines. Furthermore, many young scientists worried that an inability to do their experiments could jeopardize their careers. In an effort to bring attention to the issue, many scientists (including the two flu researchers whose research triggered the pause) formed the group Scientists for Science, which advocates against blanket bans on research. In addition, researchers were especially upset by the recommendation of the NSABB to censor the publications resulting from the experiments due to fears that this research could have a “dual use” that would threaten national security. However, not all researchers in the field support gain of function research (the opposition group is called Cambridge Working Group) and maintain that the risks of the research outweigh benefits.

The moratorium lasted until January 9th, 2017, when the OSTP released the guidelines for funding this research in the future. The new rules are essentially the same recommendations put forth by the NSABB seven months earlier. The NSABB had concluded that these studies involving “potentially pandemic pathogens” (PPP) do indeed have important benefits to public health, but warranted additional screening prior to funding approval. It directed federal agencies to create a pre-funding review mechanism using eight criteria (including whether the pathogen is likely to cause a naturally occurring pandemic, and if there are alternative methods of answering the scientific question). The results of these reviews must be reported to the White House OSTP. Importantly, the policy was implemented in the final days of the Obama administration rather than leave it to the incoming Trump administration, who, as of this date, has yet to fill nearly any top science positions, and may not have issued guidance for months, if at all.  Researchers welcomed the decision to finally lift the ban, but questioned when the projects would be allowed to resume.

What can we learn from this situation from a science policy perspective? First, we must learn not to overreact to hysteria regarding the risks of this type of research. Indeed, there are risks in performing research on potentially pandemic strains of influenza and other pathogens, as there are with other types of research. But issuing overly broad, sweeping moratoriums halting ground breaking research for years is not the answer, nor is government censorship of academic publication. While in the end, the studies were given the green light to resume, and were published without modification, there is no making up for the lost time. These studies are not machines than can simply be turned on and off on a whim without repercussions. When we delay research into learning how viruses become pandemic, we hurt our ability to detect and respond to naturally occurring outbreaks. Additionally, when American scientists are prevented from doing research that other countries are still pursuing, American leadership in the biomedical sciences is at a competitive disadvantage. (The European Academies Science Advisory Council also recently updated its recommendations for PPP research in 2015, but did not institute a moratorium.) What we learn from these studies could potentially save countless lives. Secondly, the freedom to publish without any government censorship must be valiantly defended in any and all fields, especially with a new administration with an aggressively anti-science and anti-climate stance. Lastly, the scientific community must do a better job educating the public both on the importance of these studies from a public health perspective, and on the precautions put into place to ensure that these studies are conducted safely.

In the future, there will inevitably be debates over the safety or ethics of the latest experiments in a particular field. In attempting to wade through the murky waters of a complex controversy, science policy makers should make decisions that balance public health, safety, and ethics, rather than reactionary policies like censorships and moratoriums.

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April 21, 2017 at 8:47 am

Science Policy Around the Web – September 30, 2016

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By: Jessica Hostetler, PhD

Source: Flickr, under Creative Commons

Human Genetic Manipulation

World’s first baby born with new “3 parent” technique

On September 27, 2016, the New Scientist reported the birth of a baby born with DNA from three people. The now five-month old healthy baby boy was born in New York to a Jordanian couple who had struggled for years to have a healthy child. The baby’s mother had genes for the lethal Leigh syndrome, a neurological disorder typically resulting in death in 1-3 years after birth, from which her first two children had died. These genes were carried in about 25% of her mitochondria, the energy producers for cells, which contain 37 genes separated from the thousands of other genes held inside the cell’s nucleus. Mitochondrial genes are only passed down from mothers through the mitochondria present in the mother’s egg before being fertilized by a father’s sperm.

The couple worked with US-based fertility expert John Zhang from the New Hope Fertility Center in New York City to undergo an approach for mitochondrial replacement therapy (MRT) called spindle nuclear transfer. Dr. Zhang transferred the nucleus of one of the mother’s eggs into a donor egg, which had the nucleus removed but contained healthy mitochondria. Several of these eggs were then fertilized with the father’s sperm to make 5 embryos with nuclear genes from both the father and the mother and mitochondria from the donor. The only healthy embryo was then implanted into the mother, and resulted in the birth of a healthy baby boy, with 99% healthy mitochondria.

This type of egg manipulation is now legal in the UK, though effectively banned in the US, so the team completed the fertility work in Mexico, which lacks clear regulations for the procedure. While several people such as Sian Harding who reviewed ethics for the UK guidelines, and legal scholar Rosario Isasi (from a Nature article), have acknowledged that Zhang’s group appears to have followed ethical guidelines, questions remain about the ethics, quality and safety of the technique.

The report was covered in a number of additional articles and commentaries, including in the New York Times, Science, and Nature. The commentaries note that researchers are eager for more information on a host of fronts such as the choice of using Mexico as the site of the work (as opposed to a more regulated and rigorous scientific environment) and the threshold of contaminating maternal mitochondria used in transfers (5%). These and other specifics are likely to come up when Dr. Zhang and team report on the case at the American Society for Reproductive Medicine meeting in October, 2016. (Jessica Hamzelou, New Scientist)

Health Policy

Why do obese patients get worse care? Many doctors don’t see past the fat

One in three Americans is obese; despite this fact, doctors and the healthcare system remain ill equipped in “attitudes, equipment and common practices” to treat obese patients. Beyond equipment issues, such as 90% of ERs and 80% of hospitals lacking M.R.I. machines built to accommodate very obese patients, research into bias against obese patients (both conscious and unconscious) shows that healthcare providers spend less time with such patients and refer them for fewer diagnostic tests. The same review reports that doctors feel less respect for obese patients and are more likely to stereotype them as “lazy, undisciplined and weak-willed,” all of which can negatively impact communication in the doctor-patient relationship, which in turn affects quality of care. In an effort to address the problem, the American Board of Obesity Medicine was founded to educate physicians about patient care and provide certification for achieving “competency in obesity care.”

Currently, these attitudes can lead health care providers to misdiagnose symptoms as being obesity-related instead of fully investigating other, potentially life threatening causes. Drug dosing may often be incorrect for obese people, particularly for cancer drug regimens for which obese individuals have worse outcomes across the board. Many orthopedists refuse joint hip and knee replacement surgery for obese patients unless they lose weight, though a review committee from the American Association of Hip and Knee Surgeons recommends a measured approach including options for surgery in some patients after the risks are discussed. The problems obese patients face may be exacerbated by the risk-averse hospital culture where adverse event scores affect Medicare reimbursements; thus pushing hospitals to avoid helping higher-risk patients. Beyond this there is a distinct lack of guidance from drug makers for correct dosing of anethesia drugs, with only a few examples, for instance a report from Dr. Hendrikus Lemmens out of Stanford University. Dr. Lemmens notes that 20-30% of obese-patient stays in intensive care after surgery are due to anesthetic complications and are likely frequently caused by drug dosing errors. Providing quality healthcare will likely only increase as the numbers of obese patients continue to increase in the US. (Gina Kolata, New York Times)

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September 30, 2016 at 9:00 am

Broadening the Debate: Societal Discussions on Human Genetic Editing

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By: Courtney Pinard, Ph.D.

Licensed via Creative Commons

In one of the most impressive feats of synthetic biology so far, researchers have harnessed the ability of bacteria to fight and destroy viruses, and have been able to precisely and cheaply edit genetic code using a genetic technology called clustered, regularly-interspaced short palindromic repeats (CRISPR) and CRISPR-associated endonuclease protein 9 (Cas9). CRISPR has been used to find and detect mutations related to some of the world’s most deadly diseases, such as HIV and malaria. Although CRISPR holds great promise for treating disease, it raises numerous bioethical concerns, which were sparked by the first report of deliberate editing of the DNA of human embryos by Chinese researchers. Previous blog posts have described scientific discussion surrounding the promise of CRISPR. At least three scientific research papers per day are published using this technique, and biotech companies have already begun to invest in CRISPR to modify disease-related genes. However, the use of CRISPR, or any genetic editing technology, to permanently alter the genome of human embryos is an issue of concern to a much broader range of stakeholders, including clinicians, policymakers, international governments, advocacy groups, and the public at large. As CRISPR moves us forward into the realm of the newly possible, the larger global, social and policy implications deserve thorough consideration and discussion. Policies on human genetic editing should encourage extensive international cooperation, and require clear communication between scientists and the rest of society.

There is no question that CRISPR has the potential to help cure disease, both indirectly and directly. CRISPR won the Science Breakthrough of the Year for 2015, in part, for the creation of a “gene drive” designed to reprogram mosquito genomes to eliminate malaria. Using CRISPR-Cas9 technology, investigators at the Universities of California (UC) have engineered transgenic Anopheles stephensi mosquitoes to carry an anti-malaria parasite effector gene. This genetic tool could help wipe out the malaria pathogen within a targeted mosquito population, by spreading the dominant malaria-resistant gene in 99.5% of progeny. The gene snipping precision of CRISPR can also treat certain genetic diseases directly, such as certain cancers, and sickle cell disease. CRISPR can even be used to cut HIV out of the human genome, and prevent subsequent HIV infection.

There are limitations of CRISPR, which include the possibility of off-target genetic alterations, and unintended consequences of on-target alterations. For example, the embryos used in the Chinese study described above, were non-viable, less than 50% were edited, and some embryos started to divide before the edits were complete. Within a single embryo, some cells were edited, while other cells were not. In addition, researchers found lack of specificity; the target gene was inserted into DNA at the wrong locus. Little is known about the physiology of cells and tissues that have undergone genome editing, and there is evidence that complete loss of a gene could lead to compensatory adaptation in cells over time.

Another issue of concern is that CRISPR could lead scientists down the road to eugenics. On May 14th 2015, Stanford’s Center for Law and the Biosciences and Stanford’s Phi Beta Kappa Chapter co-hosted a panel discussion on editing the human germline genome, entitled Human Germline Modification: Medicine, Science, Ethics, and Law. Panelist Marcy Darnovsky, from the Center for Genetics and Society, called human germline modification a society-altering technology because of “the potential for a genetics arms race within and between countries, and a future world in which affluent parents purchase the latest upgrades for their offspring.” Because of its potential for dual use, genetic editing was recently declared a weapon of mass destruction.

In response to ethical concerns, the co-inventor of CRISPR, Dr. Jennifer Doudna, called for a self-imposed temporary moratorium on the use of CRISPR on germline cells. Eighteen scientists, including two Nobel Prize winners, agreed on the moratorium. Policy recommendations were published in the journal Science. In addition to a moratorium, recommendations include continuing research on the strengths and weaknesses of CRISPR, educating young researchers about these, and holding international meetings with all interested stakeholders to discuss progress and reach agreements on dual use. Not all scientists support such recommendations. Physician and science policy expert Henry Miller disagrees on a moratorium, and argues that it is unfair to restrict the development of CRISPR in germline gene therapy because we would be denying families cures to monstrous genetic diseases.

So far, the ethical debate has been mostly among scientists and academics. In her article published last December in The Hill Congress Blog, Darnovsky asks: “Where are the thought leaders who focus, for example, on environmental protection, disability rights, reproductive rights and justice, racial justice, labor, or children’s welfare?” More of these voices will be heard as social and policy implications catch up with the science.

In early February, the National Academy of Sciences and National Academy of Medicine held an information-gathering meeting to determine how American public attitudes and decision making intersect with the potential for developing therapeutics using human genetic editing technologies. The Committee’s report on recommendations and public opinion is expected later this year. One future recommendation may be to require Food and Drug Administration (FDA) regulation of genetic editing technology as a part of medical device regulation. Up until recently, the FDA has been slow to approve gene therapy products. Given the fast pace of CRISPR technology development, guidelines on dual use, as determined by recommendations from the National Academies, should be published before the end of the year. So far, U.S. guidelines call for strong discouragement of any attempts at genome modification of reproductive cells for clinical application in humans, until the social, environmental, and ethical implications are broadly discussed among scientific and governmental organizations.

International guidelines on the alteration of human embryos are absolutely necessary to help regulate genetic editing worldwide. According to a News Feature in Nature, many countries, including Japan, India, and China, have no enforceable rules on germline modification. Four laboratories in China, for example, continue to use CRISPR in non-viable human embryonic modification. Societal concerns about designer babies are not new. In the early 2000s, a Council of Europe Treaty on Human Rights and Biomedicine declared human genetic modification off-limits. However, the U.K. now allows the testing of CRISPR on human embryos.

In a global sense, employing tacit science diplomacy to developments in synthetic biology may mitigate unethical use of CRISPR. Tacit science diplomacy is diplomacy that uses honesty, fairness, objectivity, reliability, skepticism, accountability, and openness as common norms of behavior to accomplish scientific goals that benefit all of humanity. The National Science Advisory Board for Biosecurity (NSABB) is a federal advisory committee that addresses issues related to biosecurity and dual use research at the request of the United States Government. Although NSABB only acts in the U.S., the committee has the capacity to use tacit science diplomacy by providing guidance on CRISPR dual use concerns to both American citizen and foreign national scientists working in the U.S.

Under tacit science diplomacy, scientific studies misusing CRISPR would be condemned in the literature, in government agencies, and in diplomatic venues. Tacit science diplomacy was used when the Indonesian government refused to give the World Health Organization (WHO) samples of the bird flu virus, which temporarily prevented vaccine development. After five years of international negotiations on this issue, a preparedness framework was established that encouraged member states to share vaccines and technologies. A similar preparedness framework could be developed for genetic editing technology.

Institutional oversight and bioethical training for the responsible use of genetic editing technology are necessary, but not sufficient on their own. Tacit science diplomacy can help scientists working in the U.S. and abroad develop shared norms. Promoting international health advocacy and science policy discussions on this topic among scientists, government agencies, industry, advocacy groups, and the public will be instrumental in preventing unintended consequences and dual use of genetic editing technology. 

Written by sciencepolicyforall

March 9, 2016 at 9:01 am