Science Policy For All

Because science policy affects everyone.

Posts Tagged ‘Malaria

Science Policy Around the Web September 13th, 2019

leave a comment »

By Neetu M. Gulati PhD

Image by mika mamy from Pixabay 

Genetically modified mosquitoes breed in Brazil

An experiment to curb the population of tropical disease-carrying mosquitoes in Brazil may have failed. In 2013 and 2015, mosquitoes with a modification called OX513A, which prevents these mosquitoes from reaching adulthood and being able to reproduce, were released into a region of Brazil. This experiment was meant to limit the spread of mosquito-borne infectious diseases that plague the area, including zika, dengue, and yellow fever. 

Initially, the goal of the genetic modification experiment was to reduce the mosquito population by 90%, which was successful during the field trial. Only about 4% of genetically modified mosquitoes were expected to be able to reach adulthood, and it was hypothesized that these mosquitoes would be too weak to reproduce. However, about 18 months after the experimental trial period ended, the mosquito population has returned to pre-trial levels. A recent study has revealed that the gene modification has been passed on in 10-60% of the mosquitoes in the area, suggesting they were able to reproduce. Furthermore, modified mosquitoes are as able to carry infectious diseases as non-modified mosquitoes. Critics of the experiment warn that not enough was known about these mosquitoes and there may be unintended consequences to the genetic modification, including a possibility of making the species more robust. The authors of the new study posited “These results demonstrate the importance of having in place a genetic monitoring program during releases of transgenic organisms to detect unanticipated consequences.”

(Fabian Schmidt, Deutsche Welle

America is in danger of losing its “measles-free” status

In 2000 the United States was declared measles-free, 37 years after the introduction of the measles vaccine in the US and Canada. Now, almost two decades later, the US is at risk of losing an official designation of “measles-elimination” status in October. This status is only given to countries without continuous measles transmission for at least one year, where cases of the disease can be linked back to a traveler who brought the virus from another place where it has been circulating. An outbreak of measles in New York state now jeopardizes this. The CDC reported over 1,200 measles cases in the US, with over 75% of the cases occurring in the state of New York. 

This is occurring because it is common in some groups to opt out of the measles vaccine. And it is not just the US; measles cases have increased around the world, and some other countries have also lost measles-free status in the last year.

The outbreak in New York can be traced back to Ukraine, which has had tens of thousands of measles cases in the last year. It then spread throughout a tight-knit community of people who chose not to vaccinate for perceived safety concerns. So while this outbreak can be linked to a traveler, many are concerned that if vaccine coverage rates continue to decline, the virus could spread enough, especially in under-vaccinated communities, that the outbreaks will begin to be “homegrown.”

(Julia Belluz, Vox)

Advertisements

Written by sciencepolicyforall

September 13, 2019 at 10:53 am

Science Policy Around the Web – April 26, 2019

leave a comment »

By: Mary Weston, Ph.D.

Source: Pixabay

World’s first malaria vaccine to go to 360,000 African children

On Tuesday, the World Health Organization (WHO) announced the launch of a large-scale pilot of the first malaria vaccine ever developed. 360,000 children under 2 years old will be vaccinated per year across three African countries (Malawi started vaccinating this week and Ghana and Kenya will began in the next couple weeks). The combined effort could immunize up to one million children by 2023. Children under five years old are at the most risk for life-threatening complications from malaria and more than 250,000 children in Africa die from the disease every year. 

The vaccine was developed by GlaxoSmithKline (GSK) and the PATH Malaria Vaccine Initiative (MVI) with support from the Gates Foundation. Data from clinical trials indicates it only provides partial protection, preventing around 40% of malaria cases. Thus, the vaccine is meant to complement existing solutions to preventing malaria ( e.g.bed nets, insecticide, and rapid diagnosis and treatment of the disease).  

Malaria is a parasitic infection that is transmitted via a bite from the female Anopheles mosquito. While the disease is preventable and treatable, an estimated 435,000 people die from it each year. The newly developed vaccine protects against P. falciparum, the most prevalent malaria strain found in sub-Saharan Africa.

The vaccine, known as RTS,S or Mosquirix, has taken decades to develop. It is given in four doses: 3 doses provided between the first five and nine months of age and the last delivered around the 2ndbirthday. While this is a big step, some malaria researchers are questioning the implementation of this vaccine when other, more effective vaccines are currently in clinical trials. However, even 40% efficacy will be very helpful in combating this devastating disease.

(Katie Hunt, CNN)

Drug Distributor And Former Execs Face First Criminal Charges In Opioid Crisis

For the first time, federal criminal charges were brought against a pharmaceutical distributer for its role in perpetuating the US’s deadly opioid crisis. Rochester Drug Co-Operative (RDC), the 6th largest distributor in the US, was charged with conspiring to distribute controlled narcotics (fentanyl and oxycodone), defrauding the United States government, and willingly failing to file suspicious order reports. Separate individual charges were also brought against two of their former executives.

Distributors connect drug makers to pharmacies and they are charged with monitoring drug distribution to ensure there is no abuse. However, this monitoring seems ineffectual at best. In one extreme example, an investigation by the Charleston Gazette Mail reported that a single pharmacy in the small town of Kermit, West Virginia (population 392) received 9 million hydrocodone pills over a two year period from out of state drug companies. 

In the RDC case, the US attorney in Manhattan, Geoffrey S. Berman, argues that greed has been the primary motivator for this abuse. Prosecutors said that RDC’s executives ignored warning signs and distributed tens of millions of fentanyl products and oxycodone pills to pharmacies they knew were distributing drugs illegally, resulting in massive profits. RDC has effectively admitted to violating federal narcotics laws and has agreed to pay a $20 million fine and will be supervised by an independent monitor over the next five years.

More than 700,000 people have died from drug overdoses over the last 20 years, the majority of which have been attributed to opioids, and some estimates predict hundreds of thousands more could die in the next decade due to opioid overdoses alone. 

Addiction treatment is underfunded in the US and the White House Council of Economic Advisers estimated that the crisis cost $500 billion in economic losses in 2015 alone. Hundreds of lawsuits across the country have been filed against opioid makers, producers, and distributors in hopes of holding them accountable, preventing misbehavior in the future, and receiving money to offset the costs of the crisis on the public. 

(Richard Gonzales, NPR)


Have an interesting science policy link? Share it in the comments!

Written by sciencepolicyforall

April 26, 2019 at 9:30 am

Science Policy Around the Web – November 20, 2018

leave a comment »

By: Andrew Wright, B.S.

NASAburningbrazil

Source: Wikimedia

 

Habitat Loss Threatens All Our Futures, World Leaders Warned

Recent reports have suggested that humanity has only 12 years to avoid catastrophic environmental collapse due to 1.5C of industrial warming. While solutions to the threat of runaway climate change have been given a new sense of urgency by these findings, there exists a commensurate and oft less visited issue, that of rapid declines in global biological diversity. Driven primarily by agricultural land conversion of terrestrial and marine ecosystems (via forest clearing and river damming, respectively), vertebrate species have declined by 60% on average since 1970 according to the World Wildlife Fund’s most recent Living Planet Report . While this decline appears strongest in South and Central America and in freshwater habitats, the report joins a compendium of literature suggesting holistic declines in biodiversity among birds, insects, fish, and terrestrial vertebrates as part of an ongoing anthropogenic mass extinction event.

To address some of the issue, the UN Convention on Biological Diversity (CBD) is currently meeting in Sharm El Sheikh, Egypt to discuss progress on the Aichi biodiversity targets for 2020.  These targets came out of The Convention on Biological Diversity, a multilateral treaty signed in 1992 focused on preserving biodiversity, sustainable use of biological resources, and equitable sharing of resources. The Aichi biodiversity targets specified that people would be aware of risks to biodiversity, and that biodiversity values would be adopted by public, private, and governmental entities by 2020. Given the rapidity, intensity, and ubiquity of the decline in species, most, if not all, of these targets will likely be missed. As such, the delegates from the 196 signatory nations will also work on creating new biodiversity targets to be finalized at the next CBD meeting in China.

Since a comprehensive solution seems necessary given the increasingly global nature of trade, authors of the new targets hope to garner a greater deal of international attention, and intend to make the case that government commitment to reversing or pausing biodiversity loss should receive equivalent weight as action on climate change.

(Jonathan Watts, The Guardian)

The Ethical Quandary of Human Infection Studies

The United States has greatly improved its ability to soundly regulate the ethics of clinical studies since the infamous malfeasance of the Tuskegee syphilis study. Most significantly, the National Research Act of 1974 established the Institutional Review Board to address how to adequately regulate the use of human subjects by adhering to the principles of respect for persons, beneficence, and justice.

The National Research Act provided a substantial step forward and provided a clear requirement for universal informed consent. However, the expansion of clinical studies to new international regions of extreme poverty, due in part to the influx of private money from large charitable organizations, has come with novel ethical considerations. In these newly explored populations where income, education, and literacy levels may be lower, emphasis is now being place on how to recruit volunteers without implicitly taking advantage of their circumstances.

One area of concern is compensation levels. While compensation in a malaria infection study in Kenya was tied to the local minimum wage, the number of volunteers recruited far surpassed expectations. This may have been due to the fact that payment during this study was guaranteed and consistent, in contrast to local work.

Aware of the concern, two of the largest private medical research funding organizations, the Bill and Melinda Gates foundation and the Wellcome Trust have recently instituted ethical guidelines putatively reinforcing the principle of beneficence, placing special emphasis on maximizing benefits over risk. It is an open question whether these protections will be sufficient, but at the very least it is important that rules to be put in place proactively rather than as a reaction.

 

(Linda Nordling, Undark/Scientific American)

 

Have an interesting science policy link? Share it in the comments!

Written by sciencepolicyforall

November 20, 2018 at 11:58 am

Science Policy Around the Web – July 25, 2017

leave a comment »

By: Allison Dennis B.S.

TopSecretMosquito

Gene Drives

With Great Power There Must Also Come–Great Responsibility!

 

On the horizon of life-changing biotechnology up for ethical debate, nestled between CRISPR and whole genome sequencing, are gene drives, which have the potential to alter genes for better or for worse across generations. During sexual reproduction each of the two versions of a gene carried by a parent has a 50% chance of being inherited by each offspring. The frequency of each version of a gene across a population is influenced by rates of mutation, migration, genetic drift, and natural selection. Gene drives present the technology to circumvent these natural forces. By introducing molecular machines capable of damaging a particular version of a gene along with the version they prefer to the cells that give rise to eggs or sperm in an organism, scientists can shift the likelihood that their version will be inherited by that organism’s offspring from 50% to 100%. Upon fertilization the undesired gene will be damaged by the molecular machine and the desired gene will used as a template to repair the damaged copy, allowing two copies of the desired gene to be permanently introduced in the offspring and inherited by the next generation. Clever applications have been proposed to design mosquitoes resistant to malaria, mice unable to transmit lyme’s disease, or salmon able to grow to full size in half the time. More bold applications would use the technology to render female mosquitoes sterile, the ultimate insecticide. However, for each one of these beneficial applications exists the devastating opposite, which could be employed to accelerate the spread of disease. Altering population genetics of one species could accidentally devastate ecosystems.

U.S. defense organizations have taken notice of this powerful technology. DARPA, the Defense Advanced Research Project Agency, has launched the Safe Genes program in an effort to anticipate and address potential risks of introducing uncontrolled or undesired gene drives. The program awarded a collective $65 million to seven labs hoping to develop counter technologies including self-fizzling drives, chemical control methods, and gene drive vaccines. This summer, to delve deep into the intellectual discussion JASON, tackled the issue. This independent group of scientists, holding stellar academic records and top-secret clearances, meets once a year to address questions posed by the U.S. Department of Energy, Department of Defense, CIA, and FBI. However, their report is likely to be classified. (Ewen Callaway, Nature News)

Violence Against Women

Beginning to Understand the Nature of Intimate Partner Violence Through Data Curation

Careful evaluation of the nature of homicides of women has revealed that 55% result from intimate partner violence (IPV). The study conducted by the US Center for Disease Control (CDC) looked into the circumstances surrounding the deaths of 10,018 women over the age of 18 between 2003 and 2014 across 18 states. In addition to cases where the victims were intimate partners of the suspect, IPV-related homicides included cases where the female victims were friends, family, or those who intervened during an incident of IPV.

Nationwide political attention was drawn to the issue of IPV starting in the 1990s. The Violence Against Women Act was passed by Congress in 1994 and sought to legally define domestic violence as a crime external to the purview of private family matters. Research has revealed several risk factors associated with intimate partner violence, including threats with weapons, stalking, obsessive jealousy, sexual assault, and controlling behavior. However, the effectiveness of political and public health interventions remain unclear due to the overall decline in violence over the last decade and believed underreporting of individual incidence.

In an effort to more broadly understand the “who, when, where and how” surrounding violent deaths that occur in the United States, including those connected with IPV, the CDC created the National Violent Death Reporting System in 2002. By pooling information gathered by local law enforcement officers, coroners, medical examiners, and state agencies the CDC is hoping learn more about “why” so many violent deaths occur, towards the goal of developing and evaluating public health interventions. At its inception, funding only supported the participation of six states. However, involvement has been increasing from 17 states in 2006 and 42 in 2016 with the goal of eventually including all 50 states, U.S. territories, and the District of Columbia.

This study confirmed that homicide as a result of IPV occurs across all age groups and racial ethnic groups. However, young black and Hispanic women are disproportionately affected compared with white and Asian women of the same age group. Overall, black and indigenous women experienced significantly higher higher homicide rates, including non IPV related cases, than women of other races. Women died as a result of the use of firearms in 53.9% of all cases. While the “why” still remains unclear, this 15 year glance back sheds some light on the groups most affected by violence inflicted by their own partners, providing opportunity for targeted prevention. (Camila Domonoske, NPR)

Have an interesting science policy link?  Share it in the comments!

Written by sciencepolicyforall

July 25, 2017 at 6:42 pm

Science Policy Around the Web – April 29, 2017

leave a comment »

By: Saurav Seshadri, PhD

digital forensics 5” by jon crel is licensed under CC BY 2.0

Forsensic Science

Now Who Will Push Ahead on Validating Forensic Science Disciplines?

The realities of forensic science remain far removed from the white-coated wizardry depicted on shows like CSI. Although forensic results often heavily influence criminal trials, there is a substantial gap between the perceived and true reliability of commonly used methods such as fingerprint and bitemark identification. The National Commission on Forensic Science (NCFS) was established in 2013 to help close this gap, by promoting rigorous, independent evaluation of forensic techniques, as well as communication between law enforcement agencies and academic scientists. The NCFS was supported jointly by the Department of Justice (DOJ) and National Institutes of Standards and Technology (NIST), and has published over forty documents reflecting the consensus of scientists, lawyers, law enforcement officers, and other stakeholders.

Recently confirmed Attorney General Jeff Sessions has decided not to renew the NCFS’ charter, which expired on April 23, 2017. Its work will ostensibly be taken over by a new entity, which will be developed by a DOJ Subcommittee on Forensics and spearheaded by an as-yet-unnamed, DOJ-appointed Senior Forensic Advisor. The DOJ is currently seeking input on how best to organize this initiative, but its actions already suggest an unwillingness to follow expert guidance, such as the original recommendations from the National Academy of Sciences that led to the creation of the NCFS. The recommendations include ‘[t]his new entity must be an independent federal agency…[i]t must not be part of a law enforcement agency’ and ‘…no existing or new division or unit within DOJ would be an appropriate location for a new entity governing the forensic science community’.

Despite this setback, some of the NCFS’ contributions, such as promoting acceptance of the need for licensing and accreditation, may have a lasting influence on the field. In the NCFS’ absence, NIST is expected to play a central role in coordinating the forensic science community. Support for these efforts will be critical to improving standards in forensic practice, and ultimately, to providing justice to the American public. (Suzanne Bell, The Conversation)

Infectious Disease

Ghana, Kenya and Malawi to Take Part in WHO Malaria Vaccine Pilot Program

While interventions such as insecticide-treated mosquito nets have dramatically reduced malaria-related deaths, almost half a million people still die annually from the disease, predominantly children in sub-Saharan Africa. Continuing the fight against malaria, the World Health Organization Regional Office for Africa (WHO/AFRO) has announced that a pilot program to test the world’s first malaria vaccine will begin in 2018. The vaccine (RTS,S or MosquirixTM) is the result of over $500 million in investment from GlaxoSmithKline and the Bill & Melinda Gates Foundation. It has shown promising results in Phase 3 trials, reducing rates of malaria by almost half in children treated at 5-17 months old. Following guidance from two independent advisory groups, the WHO will implement the vaccine in three countries that have high malarial burdens despite ongoing, large-scale anti-malaria efforts. The first stage of the program, which is being funded by several international health organizations in addition to WHO and GSK, will span 2018-2020, with final results expected in 2022.

RTS,S has followed an unconventional route to its current stage of development. It was approved by the European Medicines Agency (EMA) under Article 58, a mechanism that allows the EMA’s Committee for Medicinal Products for Human Use (CHMP) to collaborate with the WHO and international regulatory agencies to evaluate drugs intended for use in developing countries. However, in the first ten years after its inception in 2004, just seven drugs received positive opinions from CHMP through Article 58, and among these, the EMA has reported limited commercial success. This track record, combined with the emergence of more attractive incentive programs to develop drugs for tropical diseases (including a priority review voucher system launched by the FDA in 2007), has raised questions about Article 58’s effectiveness. A positive outcome for RTS,S could revitalize the program and lead to more innovative treatments for vulnerable populations worldwide. (WHO/AFRO press release)

Have an interesting science policy link?  Share it in the comments!

Written by sciencepolicyforall

April 29, 2017 at 8:56 pm

Sickle Cell Disease in Sub-Saharan Africa: Using Science Diplomacy to Promote Global Health

leave a comment »

By: Steven Brooks, PhD

         Science diplomacy is an important conduit through which nations can cooperate with each other to help address issues of common concern. Establishing international collaborations based on scientific research and resource sharing can be a valuable tool to promote advances in global health and to help foster research communities in developing nations. In 2001, Nelson Mandela proposed a model for building and advancing a network of institutions investing in Science, Engineering, and Technology (SET) across sub-Saharan Africa (SSA) to enhance economic diversification, promote job growth, and improve living conditions for peoples across the region. Since then, significant strides have been made by many international organizations, including the World Health Organization, World Bank, and United Nations, to invest in SET institutions and researchers across SSA. Much work is still needed, however, to address the significant global health disparities affecting SSA. According to the United Nations Development Programme, life expectancy in SSA is on average only 46 years. Among the largest contributory factors to this gap is HIV/AIDS, but non-communicable diseases and genetic conditions such as Sickle Cell Disease (SCD) contribute as well. SCD in particular offers a stark geographic contrast in disease outcome: in the United States, childhood mortality (up to age 18) from SCD is below 10%, while in SSA the early childhood mortality rate is 50-90% by age 5. This drastic difference in childhood mortality from SCD raises an important question- why is the difference in mortality rates so large, and what can be done to eliminate it?

SCD represents a significant public health success in the United States. From the early 1970s, average life expectancy of people with SCD has substantially increased from 14 years of age to over 40 years, and childhood mortality rates have continued to decline. These vast improvements in SCD mortality in the US are attributable to improvements in screening and early diagnosis, as well as surveillance for early childhood infections and prophylactic treatments.  Availability of therapies like hydroxyurea and access to blood transfusions have also contributed to reducing childhood mortality, while several currently ongoing clinical trials in the US are testing the use of bone marrow transplantation as a curative procedure for patients with severe complications of SCD. While the best practices for diagnosing and treating SCD are well-established in developed nations, lack of global implementation has meant that these advances in treatment have had very limited effect on reducing mortality and improving quality of life in developing nations. More than 85% of all new SCD cases occur in SSA, with over 240,000 infants with SCD born in SSA annually (compared to less than 2,000 in the US). Many nations in SSA do not have the resources or personnel to implement protocols for screening and diagnosis, and many children are born outside of hospitals. As a result, most children born with SCD in SSA will go undiagnosed, and therefore untreated, leading to devastatingly high rates of early childhood mortality for children with SCD.

The disparity in health outcomes between children born with SCD in developed nations and developing nations in SSA should be addressed through science diplomacy. An opportunity exists for diplomatic cooperation between scientists and health officials from the US and their counterparts in SSA to build infrastructure and train researchers and healthcare professionals to diagnose, treat, and innovate new solutions for SCD. The crucial first steps towards improving outcomes in SCD – parental and newborn screening, early childhood nutrition standards, parental and community education, and anti-bacterial and anti-viral vaccinations and prophylaxis – are achievable through diplomatic efforts and collaboration with governmental health agencies across SSA. Proof of this concept has been demonstrated in Bamako, Mali, with the success of the CRLD (The Center for Sickle Cell Disease Research and Control), a SCD-specific treatment and research center that reflects an effort of the government of Mali, with funding and medical resources provided by the Foundation Pierre Fabre. The CRLD utilizes modern diagnostic techniques to screen for SCD. It also provides immunizations, hospitalizations, and access to preventive medicine, and provides education and outreach to patients and to the larger community. Historically, the infant mortality rate from SCD in Mali was estimated to be 50% by age 5. Since the opening of the CRLD in 2005, only 81 of the over 6,000 patients enrolled at CRLD have died, a mortality rate for this cohort that is comparable to rates in the US and UK. The CRLD also has modern laboratories that conduct research, with over 20 academic papers published from the CRLD so far. The ongoing success of the CRLD is proof that investment in, and collaboration with, governments and medical professionals in Africa can lead to equitable health outcomes in SCD. Similar investments by the US government and the National Institutes of Health (NIH), possibly through intramural research programs, and in cooperation with health-focused private foundations, could lead to similar success stories in communities across SSA.

The NIH supports and facilitates collaborations in global health research through the NIH Fogarty International Center (FIC), which currently sponsors projects in 20 countries across SSA. NIH has also invested intramural resources into collaborations in SSA to combat Malaria. The National Institute of Allergy and Infectious Diseases (NIAID) trains and sponsors investigators to independently conduct research in Mali (NIAID’s Mali ICER (International Centers of Excellence in Research)). Despite its significant history of investment in SSA, the NIH offers almost no international support for research related to SCD. The NIH FIC only currently funds one project related to SCD, preventing pediatric stroke in Nigerian Children. The Division of Intramural Research at the NIH is currently home to robust basic science and clinical-translational research on SCD. Intramural researchers can and should collaborate with clinicians and scientists from SSA who will lead the effort to combat SCD in their home nations. More broadly, the NIH could spearhead an initiative to bring together stakeholders from the US government, health ministries from nations in SSA, and private foundations that support efforts to reduce or eradicate global disease, to begin establishing a network of laboratory and clinical facilities for testing and treatment, as well as to train clinicians and researchers from SSA in diagnostic and research techniques specific to SCD, and to design and disseminate educational resources for increasing communal knowledge regarding SCD across SSA.

In addition to significantly improving SCD mortality and health outcomes in SSA, these efforts of science diplomacy will have substantial benefits in the US as well. The US is home to a sizeable, and growing population of people living with SCD. As life expectancy continues to increase, new challenges will arise for effectively treating serious complications associated with SCD, such as renal disease, stroke, cardiovascular disease, heart failure, cardiomyopathy, and pulmonary hypertension. By collaborating with researchers and healthcare leaders studying large populations of people with SCD in SSA, the NIH will foster innovation and generate new insights about SCD that are uniquely informed by the data and perspectives of African scientists and populations. The NIH and the US government can establish a mutually beneficial program of treatment, education, and research that will enable developing nations to treat their patients with the same methods available in the US. Investing in 21st century methods of diagnosis and treatment, as well as contributing funding, training, and infrastructure to clinicians and researchers in SSA, can strengthen diplomatic relationships between governmental leaders and scientists alike and lead to lasting collaborations that strengthens research and innovation into new treatments for SCD.

Have an interesting science policy link?  Share it in the comments!

Written by sciencepolicyforall

March 3, 2017 at 9:21 am

Synthetic Biology to Cure Diseases – Promises and Challenges

leave a comment »

By: Emmette Hutchinson, PhD

       Synthetic biology is an interdisciplinary field that utilizes an engineering approach to construct novel biological products, circuits and designer organisms. This field has the potential to revolutionize many aspects of society from chemical production to healthcare. Synthetic biology holds particular promise in the production of biological therapeutics or chemical compounds for the treatment of disease. Increased efficiency and stability of production can be especially beneficial when treating global diseases that are typically associated with poverty. Treatment for these conditions is typically funded by grants from large charitable foundations, sometimes leading to scarcity as funding recedes.

In 2015, 212 million cases of malaria were reported worldwide, predominantly among the poorest countries in the world. While major initiatives such as the President’s Malaria initiative and the Gates foundation focus on various aspects of combating the disease, such as the spread of the parasite and the eradication of the disease, respectively, cost-effective treatments for infections are still needed. The most efficacious treatments for malaria are artemisinin-based combination therapies (ACTs). The 2015 Nobel Prize in Medicine was awarded in part to Youyou Tu for her work demonstrating that artemisinin, an Artemisia annua (sweet wormwood) extract, was an effective anti-malarial treatment. Landmark research published in 2006 demonstrated synthetic production of artemisinic acid, a precursor to artemisin, in yeast. Prior to this study, the only source of artemisinin was tiny hairs found on the surface of the wormwood. The supply of artemisinin has previously been unstable, resulting in dramatic price fluctuations. These price spikes have resulted in both shortages and unattainable cost of treatment. The pharmaceutical giant Sanofi licensed the yeast strain with the hope of creating a more reliable source of artemisinin. In part, due to market forces pushing down the price of artemisinin (primarily a surge in world-wide Artemisia annua cultivation), Sanofi recently sold both its technology and production facilities to Huvepharma. Despite the potential of synthetic biology to disrupt the pharmaceutical industry, this is an example of how existing production methods can impede adoption of more efficient (and stable) synthetic approaches. An alternative to synthetic production of artemisinin in yeast, termed COSTREL (combinatorial supertransformation of transplastomic recipient lines), re-creates the enzymatic pathway necessary to produce artemisinin in tobacco. Although not as efficient as synthetic production of the chemical in yeast, this route offers a significant per-acre boost in artemisinin production over the native source and a potentially more open market to supply drug manufacturers.

Similar to malaria, snake bites predominantly affect impoverished regions of the world. This makes the use of life-saving anti-venoms particularly burdensome as they are both expensive and difficult to produce. The World Health Organization estimates that up to 2.5 million cases of envenoming occur each year, resulting in death, amputations and permanent disabilities. Antivenoms are typically produced using plasma from hyperimmune animals, an often expensive and time-consuming process. In some cases, the profit margins are considered too low to continue producing effective antivenoms such as FAV-Afrique, a polyvalent antivenom effective against 10 species of sub-Saharan snakes. Two recent approaches utilizing synthetic antibody fragments have shown promising effects for protection against specific snake venoms. In a screen for antibody fragments to snake venom, Prado and colleagues found two fragments that protected mice against muscle damage from Bothrops jararacussu and Bothrops brazili venom. Ramos and colleagues designed two synthetic DNA sequences encoding components of coral snake (Micrurus corallinus) venom. Serum obtained from animals immunized with these DNA sequences resulted in 60% survival of animals given a lethal dose of coral snake venom. This second approach eliminates the need for difficult-to-obtain venom when seeking to generate hyperimmune animals as anti-venom producers. It is possible that these or similar synthetic biology approaches could be utilized to produce FAV-Afrique or other polyvalent antivenoms in a faster, more cost-effective manner than hyperimmune animals.

While the possibility of artemisinic acid-producing yeast, high artemisinin-yielding tobacco, and more efficient sources of anti-venom are compelling, regulatory challenges and ethical dilemmas are abundant in the burgeoning field of synthetic biology. Both the US and the EU have recently held surveys and drafted opinions concerning the ethics and risks of synthetic biology. One potential issue with the use of synthetic biology approaches to industrial scale production of chemicals or recombinant proteins is the potential for uncontained spread of the recombinant organism or uncontrolled transfer of the modified genetic material. Another concern centers around the impact of synthetic biology on existing biological diversity. There are also concerns regarding the proliferation of synthetic biology capabilities and biosecurity. At the moment, the United States is in middle of an epidemic of opioid addiction. Synthesis of more complex chemicals in yeast also opens up issues with substance control. A research group has already demonstrated the ability to synthesize heroin in yeast, cheaply and effectively in much the same manner as one might brew beer, raising the possibility that new, designer substances of abuse could be produced in a similar manner. Approaches to the issue of biocontainment have varied, but as the control of synthetic transcriptional circuits becomes robust, more efficacious approaches to biocontainment can be developed. One recent approach to this problem implemented a two-part genetic version of a Dead Man’s Switch into E. coli, which will kill the synthetic organism when certain conditions are not met. As a standard operating procedure, this system would go a long way toward addressing containment of engineered organisms.

The engineering of novel biologicals, re-purposing of existing or development of new transcriptional circuits and entirely new organisms holds immense promise for all aspects of society. These technologies will likely impact the treatment of diseases typically associated with poverty initially, as the increased efficiency of production will lead to stability in price and decreased scarcity of therapeutics. Once concerns of containment and potential effects on existing ecosystems are sufficiently addressed, the broad application of these technologies becomes more reasonable. As the methodologies enabling the creation of designer organisms and novel biologicals improves, the market forces that impede adoption of more efficient synthetic sources of therapeutics may also have less of an impact.

Have an interesting science policy link?  Share it in the comments!

Written by sciencepolicyforall

February 23, 2017 at 4:33 pm