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Should Vaccines be Mandatory?

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By: Juan I. Moliva, Ph.D.

Image by Angelo Esslinger from Pixabay 

The anti-vaccination movement has been gaining traction across the United States (U.S.) and the world. According to the Centers for Disease Control and Prevention (CDC), the number of measles cases in the first five months of 2019 surpassed the total number of cases per year for the past 25 years, with the number of children unvaccinated for preventable diseases quadrupling since 2001. The CDC also found an increase in the number of vaccine exemptions for kindergarteners across the U.S. While the numbers vary across the country mostly due to laws set in place by each state, in Mississippi, one of three states that do not grant exemptions due to religious or philosophical reasons, the rate of kindergartners with an exemption to one or more required vaccine was 0.1%. Compare that to Oregon, a state that grants exemptions to vaccines due to religious or philosophical reasons, where the rate of vaccine exemptions for kindergarteners is at 7.6%. As the number of individuals choosing not to get vaccinated or choosing not to vaccinate their children continues to increase, the debate as to whether vaccines should be mandatory has taken front stage.

Simply stated, a vaccine is a weakened or killed version of a pathogen that is delivered to the body with the sole goal of stimulating an immune response to protect you against the disease you are being vaccinated against. How is this accomplished? Your immune system has a subset of cells with “memory” that remember the pathogen and if you are later exposed to the pathogen these “memory” cells will eliminate the pathogen before it can make you sick. In the U.S. and most of the world, the general scientific consensus on vaccines is that they are safe and critical for maintaining healthy communities. The U.S. Senate Committee on Health, Education, Labor, and Pensions (HELP) strongly defended the case for vaccines. Chairman Lamar Alexander (R-TN) said, “The science is sound: Vaccines save lives – the lives of those who receive vaccines and the lives of those who are too young or vulnerable to be immunized.” Like any medication or medical procedure, vaccines do not come without risk, but the advantages vastly outnumber any disadvantages.

Not only do vaccines protect your body from dangerous pathogens, they also protect the community via a concept known as herd immunity. When a high enough percentage of the population is immune, pathogens have a harder time spreading. We rely on this principle to protect those who cannot receive a vaccine. However, vaccine opponents continue to argue that mandating vaccines is a slippery slope towards losing body autonomy. I have spent the last eight years studying vaccines, from basic research to pre-clinical testing through clinical trials and licensing. I have recently come to embrace the belief that the sole exemption for a vaccine that has been proven to be effective is a medical one – the case where you cannot receive a vaccine because your body responds negatively to the vaccine; this includes a weakened immune system that can be caused by chemotherapy or radiotherapy, a congenital condition that leads to an impaired immune system, or a history of serious adverse events related to vaccination such as an allergic reaction to one or more components in the vaccine.

The case against anti-vaxxers surrounds the choices they make on behalf of their children and how those choices affect their children and those in the community. If parents started claiming religious or philosophical exemptions against child safety seats or against buckling their children while driving, would we be arguing in their favor? Seatbelts and safety seats have been proven to save lives by preventing ejection from the vehicle after impact. Vaccines have been medically proven to save lives by preventing death or disability from infectious pathogens after exposure. While we expect not to be involved in a car accident, we rely on seatbelts in case we do. Vaccines work the same way; we do not want to be exposed to deadly pathogens but being vaccinated against these pathogens helps ensure we do not get sick if we do. Childrenare incapable of deciding if they want to be vaccinated as some vaccine regimens are initiated within the first year of life, thus their welfare is entrusted upon their parents. 

In the U.S. we have laws about providing proper nutrition, schooling, clothing, cleanliness, shelter, and many more that protect children’s welfare. Providing vaccines on time should be included as a basic necessity and be treated no different than other child welfare offenses. If an unvaccinated child contracts a preventable disease and is significantly affected to the point of disability or even death, the parent(s) should be directly responsible. A guardian refusing to vaccinate their medically eligible child should be treated like what it is: child endangerment. Take for example the recent case of a six-year-old in Oregon that nearly died of tetanus after sustaining a cut while playing outdoors. The child’s parents had refused to vaccinate the child with DTaP, a safe vaccine intended to protect against tetanus. The boy was held in an intensive care unit for 47 days, undergoing multiple intravenous infusions to alleviate the high fever, hypertension, and tachycardia caused by the infection. All at the cost of over $800,000 for a disease that could have been easily prevented with vaccination. Despite the episode, the boy’s parents continue to refuse the vaccine.

Although bipartisan support exists for vaccination at the federal level, it is unlikely federal law eliminating philosophical and/or religious exemptions would come to pass as public health policy is traditionally left to the states. State legislatures are beginning to introduce laws that will help limit the increase in numbers of preventable disease cases due to lack of vaccination. New York state recently passed legislation forbidding religious and non-medical exceptions to vaccines. After signing the bill, Governor Cuomo (D-NY) said, “While I understand and respect freedom of religion, our first job is to protect the public health.” Washington state, plagued by surging number of measles cases, also recently banned personal and philosophical exemptions to the MMR vaccine, which protects against measles, mumps, and rubella. Merely going to a public park or a grocery store can place unvaccinated children or immunocompromised individuals at risk of contracting a preventable disease. Such was the case of a six-year old boy with leukemia that died of measles after being exposed by his intentionally unvaccinated siblings. Senator Bill Cassidy (R-LA), a former physician, stressed: “If you are such a believer in liberty that you do not wish to be vaccinated, there should be a consequence and that should be that you cannot infect other people.” While I agree that autonomy over one’s body is important, the government has the right to require a reasonable level of vaccination for all citizens as a matter of public health. 

In the U.S. where freedom and personal liberty are valued above all else, mandatory vaccination would have a lengthy and challenging uphill battle. Additionally, data suggests that mandatory vaccination does not necessarily increase vaccination coverage. Instead, the U.S. could increase vaccinations via financial incentives similar to the system in place in Australia whereby parents receive monetary compensation when their children meet vaccination requirements. However, the most successful approach might be akin to the one the CDC implemented over sixty years ago to encourage stricter vaccination requirements by the states. By providing educational support, the CDC engaged parents, policymakers, and state and local health officials at every level to increase vaccination coverage. Education is one of the most effective ways to counter vaccination noncompliance. Specifically, educating people on the alternatives to vaccines – the morbidity and the mortality associated with lack of vaccination – was shown to be the most effective strategy. Educating why vaccines are so crucial is the most powerful weapon to combat vaccine non-compliance. 

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Written by sciencepolicyforall

August 14, 2019 at 10:00 am

Posted in Essays

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Disparity in the Global Supply and Demand for Vaccines Against Rotavirus

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By: Lawrence Wang

Image by Arek Socha from Pixabay 

Vaccines are extremely important for individual and global health. These life-saving biologics are especially important for children in developing countries, who suffer disproportionately from vaccine-preventable infectious diseases. One of these infectious diseases is rotavirus, which causes severe diarrhea and kills around 200,000 young children and babies per year1. Effective vaccines against rotavirus are responsible for saving countless lives and reducing suffering around the world.

In November 2018, the major pharmaceutical company Merck canceled a long-term commitment it made with GAVI (The Global Alliance for Vaccines and Immunization) to provide its rotavirus vaccine, RotaTeq, to four countries in West Africa (Burkina Faso, Cote d’Ivoire, Mali, and Sao Tome) for $3.50 a dose. Simultaneously, Merck increased RotaTeq shipments to China where a course sells for $40, nearly 12 times more than in West Africa2. Merck reported that the reason for this termination was “supply constraints” and an “unprecedented increase in global demand” for Rotateq3. Vaccines that were earmarked for West Africa were instead diverted to China, where they would protect millions of Chinese children while leaving millions of West African children vulnerable.

This situation exemplifies the disparity in the global supply of, and demand for, vaccines. Many vaccines are produced by large pharmaceutical companies like Merck that are based in wealthy nations (e.g., Merck’s headquarters are in New Jersey, USA). In general, developed countries have more agency in purchasing and providing vaccines for their citizens at higher prices. Developing countries, on the other hand, usually lack the money to pay for vaccines and are consequently reliant on free or subsidized vaccines. Profit-driven companies such as Merck are thus incentivized to sell their limited supply of vaccines to countries that can afford to pay more.

GAVI and UNICEF (United Nations Children’s Fund) are organizations that work to address disparities in vaccine access between industrialized and developing countries by buying and delivering vaccines to poor countries around the world4,5. However, they still rely on pharmaceutical companies to produce the vaccines that they distribute. When Merck notified GAVI and UNICEF that it would stop supplying discounted RotaTeq doses to the four West African nations, their only recourse to address the unexpected vaccine supply shortage was to help the affected countries switch to anot­­her rotavirus vaccine produced by a different company2.

This potentially problematic situation was avoided by a multilateral collaboration between aid organizations, governments, and manufacturers. Specifically, other pharmaceutical companies like GlaxoSmithKline (GSK), Serum Institute of India, and Bharat Biotech stepped in to fill the dearth left by Merck by pledging to supply their rotavirus vaccines (Rotarix, Rotavac, and Rotasiil) to the four West African countries. These countries are expected to switch to these alternative vaccines (which are actually cheaper than Merck’s) in 2020 after their supplies of RotaTeq run out6.

While this story ostensibly has a happy ending, it also highlights inherent problems in the way vaccines are supplied to the world, specifically poorer nations. These nations are reliant on aid organizations like GAVI and UNICEF to provide them with free or discounted vaccines, which are in turn dependent on profit-driven pharmaceutical companies to produce and supply the vaccines. Why can’t these multinational pharmaceutical companies, which have vast resources at their disposal, just produce more vaccines when there is a shortage?

The answer to this question is multifactorial. Firstly, vaccine production is complicated and only multinational pharmaceutical companies have the sufficient expertise, infrastructure, and manpower to produce high-quality vaccines that are safe and effective at scale. Thus, even these companies need advanced warning to produce millions of vaccine doses. Secondly, the prices for vaccines have been increasing in recent years, mostly due to high fixed overhead costs and exclusive licensing practices that preclude competition7. Thirdly, vaccines represent only about 2-3% of big pharma’s trillion-dollar production portfolio and are not the most profitable part of their portfolios8. Thus, pharmaceutical companies have little incentive to pick up the slack. How, then, can the costs of vaccines be reduced and who is supposed to step up to make vaccines when big pharmaceutical companies fall short of their obligations?

One potential solution to reduce the cost of vaccine production is for smaller pharmaceutical companies to produce generic vaccines. Generics are alternative versions of patented drugs and vaccines that are supposed to work just as well as the original formulation. In fact, India has become one of the world’s leading producers of generics and is a major source of vaccines and drugs for Africa. The issue with this solution is that the generics manufacturing industry is fraught with regulatory issues such as poor quality control and lack of oversight9. Africa is most starkly affected by these issues because manufacturers ship their lowest-quality drugs to the continent. Some of these products are completely counterfeit, with no active ingredients, while others have only a fraction of the active ingredients listed10. Without fixing quality control and oversight of generics manufacturing, this is not a viable long-term solution to provide vaccines to poor countries.

Another potential solution to increase vaccine coverage in Africa specifically would be to empower the continent to manufacture its own vaccines. Though Africa is home to nearly 17% of the world’s population, it produces less than 1% of the world’s vaccines and spends millions purchasing vaccines from foreign entities. For instance, African governments imported $900 million worth of basic vaccines for children in 201411. GAVI and UNICEF could partner with pharmaceutical companies to spearhead capacity building in specific African countries so they could produce their own vaccines, instead of making them dependent on vaccines from third parties. Apart from providing vaccines, this strategy would potentially build local biomedical capacity, provide jobs, and incentivize highly educated African expatriates to return to their home countries12.

Unfortunately, global vaccine stakeholders are hesitant to invest in building vaccine production capacity in Africa. For instance, profit-driven pharmaceutical companies tend to invest in healthy markets that will yield stable returns on their investments. Before investing in building a manufacturing facility, these companies must first ensure that the vaccines they produce will be bought for a certain price at a certain time12. Besides, It will be an uphill battle if Africa cannot produce vaccines more cheaply than other countries like India, which has already optimized infrastructure for producing vast quantities of vaccines cheaply13. Overall, there are many economic barriers that prevent Africa from developing its own vaccine manufacturing infrastructure.

In conclusion, the recent story revolving around providing rotavirus vaccine for West African countries exemplifies the complex challenges in supplying vaccines for the world, especially developing countries that contain some of the world’s most vulnerable populations. Despite the relatively vast resources that global organizations and companies like GAVI, Merck, GSK, and UNICEF have at their disposal, the demand for life-saving vaccines continues to outstrip the supply of vaccines. The bottom line is that vaccines are a vital component to the health of people and nations, and access to these medicines ought to be a universal human right.

  1. https://www.who.int/immunization/diseases/rotavirus/en/
  2. https://www.npr.org/sections/goatsandsoda/2018/11/01/655844287
  3. https://www.fiercepharma.com/pharma/amid-china-launch-merck-cites-supply-limits-plan-to-scale-down-rotateq-shipments-africa
  4. https://www.gavi.org/
  5. https://www.unicef.org/
  6. https://www.npr.org/sections/goatsandsoda/2019/05/31/726863111/it-looked-as-though-millions-of-babies-would-miss-out-on-a-lifesaving-vaccine
  7. https://www.who.int/immunization/programmes_systems/procurement/market/en/
  8. https://www.theatlantic.com/business/archive/2015/02/vaccines-are-profitable-so-what/385214/
  9. https://www.statnews.com/2019/07/22/indian-pharmaceutical-industry-drug-quality-charges/
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105729/
  11. https://www.dw.com/en/africa-wants-to-manufacture-its-own-vaccines/a-46151389
  12. https://www.frontiersin.org/articles/10.3389/fpubh.2019.00056/full
  13. https://www.thehindu.com/sci-tech/health/trusting-the-science/article25861183.ece

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Written by sciencepolicyforall

August 7, 2019 at 2:45 pm

Where to have a baby? Newborn screening is not created equal.

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By: Emily Wires, Ph.D.

Image by PublicDomainPictures from Pixabay 

In 2017, there were an estimated 3,855,500 live births in the United States, one of whom was my son. Within the first days of life, infants are tested for heritable disorders that can hinder physical and/or cognitive development. Unfortunately, the same set of potentially life-saving tests are not equal for all 3,855,500 infants. 

Since its conception in the 1960ss, newborn screening has been recognized as an essential preventative public health initiative. Serving as a frontline for early detection, conditions included on the screening panel are often considered rare and early intervention is essential to improved quality of life. The Newborn Screening Saves Lives Act was signed into law in 2008 and sought to bring public awareness among parents and health professionals as well as improve newborn screening programs.   

Currently, the panel of tested disorders varies state to state — yes, that means your baby’s health trajectory can be influenced by state lines. When considering birth location, most expecting parents grapple with the pros and cons of hospital versus birthing center versus home birth, but many are naïve to state regulations. Newborn screening standards, specimen collection, and follow-up procedures are implemented by state health departments. Contact information for newborn screening laboratories and follow-up program are available for individual states. Variations in statutes often extend beyond the panel of testable conditions, spilling over to funding for both screening programs and treatments, laboratory standards, and parents’ rights of refusal. To address discrepancies among states, the Department of Health and Human Services (HHS) has provided a Recommended Uniform Screening Panel (RUSP) that includes 34 core conditions and 26 secondary conditions and serves as a suggestive resource for state governments to incorporate as part of their screening programs. RUSP inclusion criteria stipulates a condition be identifiable 24-48 hours following birth, screening tests for the condition are available and validated, and the condition has been shown to benefit from early detection. Conditions included within RUSP are recommended by the Advisory Committee on Heritable Disorders in Newborns and Children along with the HHS Secretary. Despite these recommendations, not all states adhere to RUSP suggestions. 

Orphan drugs are intended to serve the rare disease community but are often commercially underdeveloped owing to their limited profitability. The Orphan Drug Act, passed in 1983, has since served as a legislative springboard set to improve the lives of individuals with rare diseases by incentivizing and accelerating drug discovery. Rare diseases are just that– rare, and because rare diseases are defined as disorders that affect less than 200,000 Americans at one time (with a sizeable proportion belonging to pediatric populations), pharmaceutical companies often expect to incur financial loss developing orphan drugs, which often means a treatment is not pursued. Collectively, however, rare diseases comprise a large healthcare need (an estimated 30 million people in the US are living with a rare disease) and have garnered increased public interest through the work of patient advocacy groupsresearch institutionsgrant funding opportunities, and public events such as Rare Disease Day

So, herein lies the dilemma. Are we essentially running a relay race but missing the handoff? Newborn screening assesses the presence of heritable conditions during a critical development period that otherwise may be missed and parallels an incentivized impetus for drug discovery, yet many states are dropping the proverbial baton regarding panel legislation. Consider, Spinal Muscular Atrophy (SMA) and its recent headlines in the rare disease community. SMA is a debilitating (and deadly), heritable disorder resulting in the loss of motor neurons and subsequent muscle atrophy. In 2016, the Food and Drug Administration approved Spinraza as the first-ever treatment of SMA. The American Academy of Neurology 2019 annual meeting recently reported data from 25 infants diagnosed with SMA at less than six weeks of age who received Spinraza prior to observable symptoms. By 14-34 months, none of these infants required permanent ventilation, all were able to sit and swallow without support, and most of them could walk on their own. However, despite this monumental advancement, not all states include SMA in their newborn screening panel. 

How do we become better for the rare disease community? Admittedly, a loaded question and likely multifaceted in approach. One potential approach would be to federally incentivize universal newborn screening across states. Screening implementation conditions typically vary due to financial constraints, frequency of disorder within state’s population, and treatment availability. California and Pennsylvania are currently the only states that with rare disease legislative caucuses. These bipartisan committees are comprised of individuals dedicated to bridging awareness among policy makers, scientists, patients, and the public. However, there are still discrepancies even among states with caucuses (California tests for 63 conditions, while Pennsylvania tests for 38), attesting to the critical necessity of a universal screening panel. 

Science is making vast strides in the detection and treatment of rare diseases. It is time for public health and policy makers follow suit in an appropriate manner, especially when time may be a crucial factor for our youngest rare disease patients

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Written by sciencepolicyforall

August 2, 2019 at 2:38 pm

Homegrown Apocalypse: A Guide to the Holocene Extinction

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By: Andrew Wright BSc

Homegrown Apocalypse: A Guide to the Holocene Extinction

One of the unifying factors of mass extinctions is a rapid change in global average temperature. The end-Ordovician extinction, the second largest, occurred when newly forming mountains made of silicate rock quickly absorbed atmospheric CO2. The global average temperature plunged, leading to the formation of enormous glaciers, drastically lower ocean levels, and much colder waters. Since complex life was still relegated to the oceans, this killed 86% of all species. The most well-known extinction is the end-Cretaceous or K-Pg event caused in part by a massive asteroid impact in Chicxulub, Mexico. The immediate impact, roughly one billion times stronger than the atomic bombings of Japan, was devastating in its own right. However, the subsequent ejection of sulfate-bearing rock into the atmosphere was the real killer, dropping global temperatures by 2-7°C, inhibiting photosynthesis, and acidifying the oceans. Coming right after a period of global warming, this extinction killed about 76% of all species.

            These extinctions pale in comparison to the end-Permian extinction, also known as the Great Dying. When Pangea was the sole continent, an enormous pool of lava called a flood-basalt plain slowly erupted over what is modern-day Siberia. Over 350,000 years, magmatic rock up to a mile thick solidified and covered an area roughly half the size of the United States. This igneous cap forced underground lava to move sideways and spread in paths called sills. As the lava traveled, it vaporized increasing amounts of carbonates and oil and coal deposits, leading to an immense build-up of CO2. Once the sills reached the edge of the cap, these gases were violently expelled, ejecting up to 100,000 gigatons of CO2. The immediate effect was a global average temperature increase of roughly 5°C. Subsequently, oceanic methane hydrate (or methane clathrate) crystals, which become unstable at high temperatures, broke down. Since methane is 20-80 times more potent than CO2as a greenhouse gas, global average temperature increased a further 10°C, bringing the total to 15°C. This left the planet barren, desertified most of Pangea, strongly acidified the oceans, killed 96% of marine life, and 90% of all life on Earth.

            We are currently living through the beginnings of the sixth mass extinction event, known as the Holocene. Species are dying off 10-100 times faster than they should and that rate is accelerating. Insects, including pollinators, are dying off so quickly that 40% of them may disappear within decadesOne in eight birds are threatened with extinction, 40% of amphibians are in steep decline, and marine biodiversity is falling off as well. At current rates, half of all species on Earth could be wiped out by the end of the century. 

What is the commonality between our present circumstances and the past? As with previous mass extinctions, global average temperature has increased. Since 1880, global average temperature has increased by 0.8°C and the rate of warming has doubled since 1975. This June was the hottest month ever recorded on Earth, with global average temperature reaching 2°C above pre-industrial levels. Greenland lost two billion tons of ice in one day. This increase in temperature is because we are currently adding 37.1 gigatons of CO2 per year to the atmosphere, and that number is rising

            From the most recent International Panel on Climate Change (IPCC) report, we know that the best outcome is to keep the increase in global average temperature below 1.5°C. Instead, let us consider what would happen if current trends stay the same and CO2 emissions continue to increase at similar rates until 2100. This is known as the RCP 8.5 model. Under this paradigm, atmospheric CO2 levels will rise from 410 parts per million (ppm) to 936 ppm. The global average temperature will increase by 6°C from pre-industrial levels. That puts the Earth squarely within the temperature range of previous mass extinction periods. 

Given this level of warming the following can be expected to occur: first and foremost, the extreme heat on the planet will massively decrease glaciation, causing a surge in ocean levels. Since water expands as it gets warmer, ocean levels will increase even further to about 12ft higher than current levels. This means most coastal areas will perpetually flood while others will be completely underwater. Unfortunately, non-coastal areas won’t be free from hardship as high air temperature will cause desertification, crop die-off, drought, and widespread wildfires. Secondly, as the ocean absorbs CO2 from the atmosphere, it will become increasingly acidic. So far, the pH of the ocean has only changed by 0.1, but under an RCP 8.5 model, that decrease could be as high as a 0.48 reduction in pH. Since this measurement is on a logarithmic scale, this means that the oceans will be acidic enough to break down the calcium carbonate out of which shellfish and corals are built. Warmer water cannot hold oxygen as effectively as cold, meaning many water-breathing species will suffocate. In combination, these two factors will serve to eliminate a huge source of the human food supply. Finally, since weather patterns are based on ocean and air currents and increasing temperatures can destabilize them, massive hurricanes, dangerously cold weather systems, and flood-inducing rainfall will become the norm. 

One parallel to the end-Permian extinction might result as well. Over millions of years, methane clathrate re-stabilized in the permafrost of Siberia and in the deep ocean floor. But in what has been termed the clathrate gun hypothesis, if methane clathrate destabilizes again at high temperatures, then the resultant methane emissions and planetary warming could form a positive-feedback loop, releasing even more crystallized methane until we end up in another “great dying”. While short-term warming probably won’t cause a runaway temperature increase, a 6°C increase in global average temperature might. New research suggests methane release may not even be necessary as the ocean is reaching a critical point in the carbon cycle where it could rapidly expel an amount of CO2on par with flood-basalt events. Moreover, like the end-Permian extinction, anthropogenic climate change is occurring on a near instantaneous geological time scale and species, including our own, will not have the requisite time to adapt.

Of course, none of these effects exists in a vacuum. They will be alongside increasing deforestation for agriculture, plastic and chemical pollution, and resource extraction. The end result would be a planet with less space, little food, mass migration, and devastating weather. So, what can be done to stop this scenario from coming true? The latest IPCC report essentially places humanity at an inflection point. Either CO2output is cut in half by 2030 and humans become carbon neutral by 2050, or the planet is irrevocably thrust past the point of no return. 

This timeframe may seem short, but it takes into account that even if civilization were to completely stop emitting greenhouse gasses today, it would take hundreds of years for global average temperature to  go back down since it takes time for the ocean to absorb CO2from the atmosphere. Like any problem of scale, there is no one solution to reaching carbon neutrality and it will take a multivariate approach. Some solutions include enacting carbon tax measures, subsidizing and implementing renewable energy (while divesting from new coal and oil production), an increased reliance on nuclear power, large-scale reforestation, livestock reduction, and carbon-sequestration technology. Some of these efforts have come a long way and some have gone in the wrong direction.

This is, of course, a global problem to be solved. At a time when the United States has signaled its intention to withdraw from the Paris Climate Accord as soon as possible and states are rejecting carbon cap-and-trade measures, other nations are moving ahead with unprecedented boosts in renewable energy and bold commitments to reducing greenhouse gas emissions. India, the third-largest polluter after the United States, is on track to surpass its Paris Accord commitments. Should the United States re-engage with and lead the international effort to tackle what is an existential threat, then it is not improbable that the end of this century could be a pleasant one. So, if the idea of living through a global extinction event is disconcerting, one can be assured that the problem is still just barely a solvable one. 

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Written by sciencepolicyforall

July 11, 2019 at 4:24 pm

How human health depends on biodiversity

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By: Lynda Truong

Image by V Perez from Pixabay 

By many measures, the Earth is facing its sixth mass extinction. The fifth mass extinction, a result of a meteorite approximately 10 km in diameter, wiped out the dinosaurs and an estimated 40-75% of species on Earth. This time around, the natural disaster that is threatening life on Earth is us.

In May, the United Nations released a preliminary report on the drastic risk to biodiversity (not to be confused with the recent report on the drastic consequences of climate change).  The assessment, which was compiled by the Intergovernmental Science-policy Platform on Biodiversity and Ecosystem Services (IPBES), draws on information from 15,000 scientific and government sources with contributions from 145 global experts. It projects that one million species face risk of extinction. Scientists have estimated that the historical base level rate of extinction is one per million species per year, and more recent studies suggest rates as low as 0.1 per million species per year. At the established base level rates, it would take one to ten million years to see the same magnitude of extinction the planet currently faces. This accelerated rate of extinction can be linked to a variety of man-made causes, including changes in land and sea use, direct exploitation of organisms, climate change, pollution, and the introduction of invasive species. 

For some, that may not seem important. If humans are not on the endangered species list, why should it matter? As the IPBES Global Assessment indicates however, healthy ecosystems provide a variety of services, including improving air quality, purifying drinking water, and mitigating floods and erosions. The vast canopies of rainforests worldwide sequester 2.6 billion tons of carbon dioxide a year. Plants and soil microbes found in wetlands can remove toxins from water, including explosive chemicals such as nitroglycerin and trinitrotoluene (TNT). Mangrove forests serve as an important buffer against ocean storm surges for those on land. Nature is a powerful resource, and declines in biodiversity have broad implications for global development and health. 

The importance of biodiversity on global health is immediately apparent in middle- and low-income countries, which rely heavily on natural remedies and seasonal harvests for health and nutrition. The loss of entire species of plants can eliminate valuable sources of traditional medicine for indigenous communities. Genetically diverse crops are more resilient to pest and disease, ensuring a stable food supply and bolstering food security. Beyond this, ecosystem disturbances also have complex implications for infectious disease, which are often endemic to developing nations. 

However, these effects are also seen in first world countries. A well cited example for the impact of biodiversity loss on infectious disease involves Lyme disease, which is endemic to parts of the United States. The white footed mouse is a common carrier of Lyme disease, and in areas with high densities of these mice, ticks are likely to feed on the mice and subsequently transmit the disease to humans. However, the presence of other mammals that the tick can feed on dilutes the disease reservoir, lowering the likelihood of an outbreak (commonly referred to as the “dilution effect”). While biodiversity has complicated effects on the spread of infectious diseases, drastic changes to ecosystems often provide a breeding ground for disease vectors and lead to increases in transmission.

In addition to the direct effects of declines in biodiversity have on global health, an often-neglected aspect of its importance for health is as a resource for biomedical science. The IPBES assessment reports that 70% of cancer drugs are natural or inspired by natural sources such as traditional medicines. This merely scratches the surface of the influence of nature on modern biomedical research. 

Much like the communities that rely on natural products as medicine, many drug compounds produced by pharmaceutical companies are derived from nature. Morphine has been one of the most revolutionary drug compounds in history, effectively treating both acute and chronic pain. The compound was originally isolated from the opium poppy, and its chemical structure has since been modified to reduce negative effects and improve potency. While the current opioid crisis in the United States has highlighted the importance of moderate use, morphine and its analogues are some of the most useful and reliable pain relievers in modern medicine. Similarly, aspirin has been regarded as a wonder drug for its analgesic, anti-inflammatory, and cardioprotective effects. Aspirin is a chemical analogue of salicylic acid, a compound originally isolated from willow tree bark. 

Beyond general pain relief, many naturally derived drugs have also been useful for disease treatment. Quinine, the first effective antimalarial drug, was extracted from the bark of cinchona trees, and quinine and its analogues are still used to treat malaria today. Penicillin, serendipitously discovered in a fungus, has been useful for treating bacterial infections and informing modern antibiotic development. These medicines and many more have been crucial to the advancement of human health, yet could have just as easily been lost to extinction.

On a more fundamental level, scientific research has benefited from many proteins isolated from nature. Thermophilic polymerases, isolated from a bacterium residing in hot springs, are now an essential component of polymerase chain reactions (PCR) – a common laboratory technique that amplifies segments of DNA. This method is critical in molecular biology labs for basic research, and forensic labs for criminal investigations.Fluorescent proteins, which have been isolated from jelly fish and sea anemone, revolutionized the field of molecular biology by allowing scientists to visualize dynamic cellular components in real time. More recently, CRISPR/Cas systems were discovered in bacteria and have been developed as a gene editing tool capable of easily and precisely modifying genetic sequences. These basic tools have vastly improved the scope of biomedical research, and all of them would have been close to impossible to develop without their natural sources.

In addition to medicines and tools, nature has often informed biomedical research. Denning bears are commonly studied for potential solutions to osteoporosis and renal disease. Their ability to enter a reduced metabolic state where they do not eat, drink, or defecate for months at a time provides valuable insight into how these biological processes may be adapted to benefit human disease and physiology. Even more interestingly, there are a few species of frogs that become nearly frozen solid in winter, and thaw fully recovered in spring. In this frozen state, much of the water in their body turns to ice, their heart stops beating, and they stop breathing. When temperatures rise, they thaw from the inside out and continue life as per usual. Crazy cryonics and immortality aside, the freeze/thaw cycles could inform improved preservation for organ transplants.

Nature is a much better experimentalist than any human, having had billions of years to refine its experiments through the process of evolution and natural selection. Depleting these living resources, which provide invaluable benefits to human health and ecosystems, lacks foresight and is dangerously reckless. The techno-optimist approach of ceaseless development in the blind belief that whatever problem humanity encounters can be solved with research and innovation neglects to account for the dependency of research and innovation on nature. Most biomedical scientists, most physicians, and much of the general public have probably devoted a minimal amount of consideration to the importance of biodiversity. But for the one million species currently at risk, and for the hundreds of million more yet to be discovered, it’s worth a thought.

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Written by sciencepolicyforall

June 7, 2019 at 9:51 am

Gene editing- Regulatory and ethical challenges

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By: Chringma Sherpa, Ph.D.

Image by Colin Behrens from Pixabay 

When power is discovered, man always turns to it. The science of heredity will soon provide power on a stupendous scale; and in some country, at some point, perhaps, not distant, that power will be applied to control the composition of a nation. Whether the institution of such control will ultimately be good or bad for that nation, or for humanity at large, is a separate question.

William Bateson, English biologist who coined the term “genetics.”

On November 25, 2018, in an allegedly leaked YouTube video, He Jiankui, a scientist at the Southern University of Science and Technology in Shenzhen, China, revealed the birth of the first gene-edited babies using a technology called CRISPR. There has been a general consensus in the scientific community that heritable changes should not be made to prevent the off-target and unwanted genetic changes artificially produced in an individual during gene editing to be passed on to his/her offspring(s). He became the first scientist to publicly violate this consensus resulting in an international scandal and criminal/ethics investigations into both He and his collaborators.

In the wake of He’s CRISPR-babies scandal, scientists worldwide are debating on the ethical and regulatory measures that would discourage another wayward and rogue scientist like He from attempting such an irresponsible feat.  At the 2nd international summit on human gene editing that convened two days after He’s video became public, He presented his work. The summit was well attended by ethicist and journalist besides scientists. At the summit, David Baltimore of the California Institute of Technology, who chaired the organizing committees for both the 1st and 2nd international summits on human gene editing read one of the conclusions from the 1st summit held at Washington DC in 2015 – “It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application”. Baltimore called He’s work outright irresponsible on the basis of the statement from the 1st summit. At the summit, many other ethical and safety-related questions were raised which He failed to answer or did not answer convincingly. 

He’s scandal has driven various organizations to draft new guidelines and sanctions aimed at preventing unethical and unapproved use of genome editing.  China has imposed new laws requiring human gene editing projects to be approved by China’s health ministry first to avoid fines and blacklists. Both the 2nd human gene editing summit and the WHO panel that convened in March 2019, have proposed a central registry of human gene-editing research and called for an international forum/ committee to devise guidelines for human gene editing based on common norms and differences of opinions between countries.  To allow time for the creation and effective implementation of new regulations, the WHO also called for a global moratorium on heritable editing of human eggs, sperm, or embryos for the next five years. Supporting the WHO panel’s recommendations, Francis Collins, director of the National Institute of Health, said that “NIH strongly agrees that an international moratorium should be put into effect immediately”. However, not all scientists are in favor of a moratorium, as they believe it might stifle the growth of a technology that might be safe and beneficial in the near future. Jennifer Doudna of the University of California, Berkley, one of the co-inventors of CRISPR gene editing, says that she prefers strict regulation that precludes the use of germline editing until scientific, ethical, and societal issues are resolved over a moratorium. David Baltimore agrees with Doudna stating that the word moratorium was intentionally not used in both the human gene editing summits as a moratorium would be hard to reverse.  Science historian Ben Hurlbut of Arizona State University, who had numerous discussions with He before Lulu and Nana were created, thinks a blanket moratorium on clinical germline editing would have prevented He from proceeding. Both the two human gene editing summits and a 2015 essay by Baltimore, Doudna, and 16 co-authors had already outlined numerous guidelines for clinical germline editing. According to Hurlbut, He weighed these criteria and believing that his procedure met all the guidelines proceeded. A categorical prohibition of germline editing would not have allowed him to use his subjective judgment and act out of self-interest. 

The modern debate over CRISPR editing is not the first time the scientific community has come together to discuss game-changing biological technologies, and it is heavily informed by two prior events. In 1970, Paul Berg and his postdoctoral researcher David Jackson used the recombinant DNA technology to create the first chimeric DNA. This invention created an uproar among the scientists and the general public who feared that this technology would lead to the creation of uncontrollable and destructive superbugs, the exaggerated versions of which can be seen in some science fiction movies. Yielding to the opinions and sentiments of the fellow scientists, Berg held himself from cloning such recombinant DNAs and in 1974, he pleaded for a voluntary moratorium on certain kinds of recombinant DNA research until their safety issues have been resolved.  He also moved quickly to organize the Asilomar conference (Asilomar II) in 1975 that bore semblance to the 2nd human gene editing conference in that it invited not only the scientists but lawyers, ethicists, writers, and journalists to weigh in on the risk-benefit analysis of the Recombinant DNA technology. On the recommendation of Asilomar conference, Donald Fredrickson, then director of the National Institutes of Health (NIH), initiated the formation Recombinant DNA Advisory Committee (RAC) to act as a gatekeeper of all research that involved recombinant DNA technology. The scope of the committee, which was composed of stakeholders, including basic scientists, physicians, ethicists, theologians, and patients’ advocates was later expanded to encompass the review and approval of human gene therapy research. Due to the redundancies of regulatory oversights between the US Food and Drug Administration (FDA) and RAC, RAC was reinstated as only an advisory body providing advice on the safety and ethical issues associated with emerging biotechnologies in 2019.

While this is a successful example of scientific self-regulation, the second event resulted in a major setback in the field of gene therapy. On September 13, 1999, Mark Batshaw and James Wilson of University of Pennsylvania supervised the administration of adenovirus to an 18-year-old Jesse Gelsinger in a gene therapy clinical trial. Gelsinger died of liver and kidney failure and brain damage three days later. Like the birth of CRISPR babies, Gelsinger’s death was an instance where new technology was used prematurely without a thorough assessment of its safety profile. It is suspected that both the clinical applications headed by He and Wilson might also have been motivated by fame and financial gain; He and Wilson both had financial stakes in private biotechnology companies that would benefit from these human trials. In the aftermath of Gelsinger’s death, Wilson was banned from carrying out FDA regulated clinical trials for the next five year, nearly all gene therapy trials were frozen, and many biotechnology companies carrying out these trails went bankrupt. This was a dark period in the history of gene therapy, and it would take almost another decade of introspection, reconsideration, and more basic experimentation for gene-therapy to re-emerge as a viable therapeutic strategy.

Figure 1: The regulatory status of human germline gene modification in various countries. Thirty-nine countries were surveyed and categorized as “Ban based on legislation” (25, pink), “Ban based on guidelines” (4, faint pink), “Ambiguous” (9, gray), and “Restrictive” (1, light gray). Non-colored countries were excluded in this survey. Adapted from Araki, M. and Ishii, T (2014): “International regulatory landscape and integration of corrective genome editing into in vitro fertilization” Reproductive Biology and Endocrinology, 2014 12:108

Scientists at both the Asilomar and human gene editing conferences passionately debated the safety of the relevant technologies but deliberated on the discussion of the big ethical issue associated with these technologies – the ultimate creation of designer babies. That gene editing sits on the slippery slope to eugenics was recognized since the days of Charles Darwin and Gregor Mendel when the study of genes and heredity was still in its infancy and the discovery of DNA as the genetic material was half a century away. One of the earliest proponents of genetic manipulation for human benefits was Francis Galton, Charles Darwin’s cousin. Galton proposed an unnatural and accelerated selection of beneficial traits by marriage between people of desirable traits. The danger that someday some rogue scientists might use germline gene editing technology in favor of eugenics lurks in the mind of those who understand the potential of the currently available gene editing technologies. However, more fearful is the idea that the wave of positive eugenics would soon give way to negative eugenics – elimination of undesirable traits as it did around World War II as exemplified by the famous case of Carrie Buck, a woman who was designated “mentally incompetent” and involuntarily sterilized. 

Various countries have their own regulation and legislation on germline editing to prevent any backlash from this powerful technology. Figure 1 presents a summary of the regulatory landscape of germline gene modification surveyed in thirty-nine countries by Araki Motoko and Tetsuya Ishii.  In the US, Congress has shown strong support against germline gene editing. In 1996, it passed a rider as part of the annual appropriations bill that prohibits the use of federal funds for any research involving human embryo. In another appropriations bill passed in 2015, Congress banned the FDA from considering applications involving the therapeutic modification of the human germline. 

Human gene editing holds great promises in treating many life-threatening and previously intractable diseases. Only when this discipline of science is held to high ethical standards and regulated sensibly at international, national, and a personal level, shall we reap the benefits of this powerful technology.

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May 29, 2019 at 9:25 am

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How are we welcoming our next generation-The first 1000 golden days?

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By: Deepika Shrestha , Ph.D.

Source: Wikimedia

The most important period for a child’s development, especially for the brain and immune system, is the first 1000 days of life. The Developmental Origins of Health and Disease (DoHAD) hypothesis suggests that the roots of many complex diseases and behavioral risks originate very early – between the time window of pre-conception to early postnatal periods. Indeed, genetic, epigenetic and environmental evidence indicate that most adulthood health and disease risk have been coded during fetal development in the intrauterine environment, lending support for the DoHAD hypothesis

The increased prevalence of an obesogenic environment and rate of chronic diseases in mothers increases the risk of childhood obesity and future cardiometabolic risk in the offspring. Moreover, increased risks can be transgenerational within families. This is also the case for Autism, Attention Deficit Hyperactive Disorder (ADHD), and other mental and psychological disorders. Given that over 50% of all mothers are overweight or obese, there is a growing cause of concern about the quality of fetal growth and development. Further, recent statistics revealed a sobering picture of increased incidence of various maternity-related illnesses such as postpartum depression (CDC Reports: as high as 1 in 5 women) and maternal mortality (CDC MMR 2019 report: 700 deaths per year- out of which relatively 3 in 5 deaths preventable, 31.3% deaths occurred during pregnancy, 16.9% on the day of delivery, and 51.8% over 1 year of post-partum days) in the US. These numbers show that many women in the US are among the most vulnerable and need sufficient support from family, society and governmental policy. There have been successful campaigns to institute policies raising awareness of issues concerning fetus growth, development and maternal/infant nutrition in developing countries, such as Golden 1000 Days. The United States needs similar programs special focusing on maternal care, especially on the nutritional, psychological, mental and financial needs of pregnant mothers and women in reproductive age groups. 

Another program has also been put in place to improve nutrition in mothers and children. The Women, Infant and Child (WIC) program provides supplemental nutritional support to roughly 8 million low-income mothers and young children under 5 years of age. With approximately 6 billion USD of funding in 2016, the current WIC program is the result of an update in 2009 after rigorous review by the Institute of Medicine (IoM) to reflect the latest nutritional science as well as public health concerns. However, recent evidence indicates that food and nutrients supplements through the WIC program might not match the nutritional need of the participants as it fails to account for women’s prepregnancy obesity status, gestational weight gain, and gestational diabetes.  For instance, concentrated fruit juice may increase the risk of gestational diabetes risk and is not a healthy food option. This important policy needs fair re-evaluation based on the updated scientific evidence for nutritional needs.

Another point of concern for expecting mothers is the lack of psychological care. Mothers-to-be undergo extensive physiological and psychological changes during pregnancy. Therefore, this 1000-day window is a sensitive time period —a time where pregnant women require support and potential intervention. Recent data highlight increasing trends of maternity related illnesses, be it postpartum depression or maternal mortality. More importantly, in the US these issues disproportionately affect women of color or low socioeconomic status.  Alarmingly, 42% of mothers  are sole or primary earners and may lack adequate financial support from their spouse and family. The Pregnancy Discrimination Act and Family and Medical Leave (FMLA) act was put in place to protect pregnant women in the job place for 12 weeks after childbirth. However, the United States is one of the few countries in the world with almost no access to paid parental leave—only 14% of civilian workers have access to any amount of paid parental leave in 2016, a slight increase from 11% in 2010

Access to paid parental leave currently serves as elite benefits and is dependent upon company policy. The most generous policies afford 16 weeks for birth mother, 8 weeks for birth father, 8–16 weeks for adoptive parents (16 for primary, 8 for secondary) according to PL+US’s report. About 23% of mothers go to work within 10 days of giving birth and are disproportionately from low-income families.In addition to maternal paid leave, recent mothers often require considerable sick leave for the first year, and providing a flexible policy could be a steppingstone towards helping the psychological as well as physiological health of a child. Furthermore, it is no secret that inspected and reputable day care facilities takes a major chunk of the family income, and are unaffordable to many families.

In addition, there is also a need for Newborn Rights. Irrespective of socioeconomic status, each baby has inborn rights and deserve equal family bonding time and breast-feeding needs. Children born to poor maternal care during pregnancy and lactating period are at increased risk of having neurological problems, poor school achievement, early school dropout, low-skilled employment, and providing poor care to their own children, thus contributing to the intergenerational transmission of poverty and malnutrition. On the contrary, children who get good nutrition and care in their first 1000 days are ten times more likely to overcome life threatening childhood disease, have higher educational retention in schools and are likely to earn more than 21% in wages as adults and also to have healthier families on their own. Therefore, there is an unmet need for a stronger policy that invests in children and their families from the very beginning and helps each child to be a healthy and contributing member of the society in their adulthood. It takes a major process and significant effort to raise a child into a healthy adult who is mentally, spiritually and physically fit to keep going in a productive society.

Paid maternity leave and insurance coverage needs support from Government/Congress to mothers or family unit regardless of the beneficiary’s work status. Investing in this policy may cost taxpayer a small percent of GDP (Gross Domestic Products) but will have a huge return in the long run when Health is valued as development index. There is ample evidence to show that countries that fail to invest in the well-being of women and children in the first 1,000 days lose billions of dollars to lower economic productivity, health issues, societal inequality and higher health costs. This is a main point of concern given that the US is lagging far behind other developed nations in this human development index (HDI). Currently, there is a huge disparity of investment in the first 1000 days based on socioeconomic status, and there is a clear and unmet need for structural and policy intervention. Issues related to the maternity period such as nutritional aspect, mental health, and paid maternity (or paternity) leave should not be considered only a women’s issue. Therefore, more than ever, there is a heightened need for research resources to understand maternity health issues and also concrete plans to address these issues.

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Written by sciencepolicyforall

May 24, 2019 at 2:21 pm