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How Science Policy Affects Pandemic Pathogen Research

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By: Samuel Porter, PhD

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

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

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

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

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

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

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

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Written by sciencepolicyforall

April 21, 2017 at 8:47 am

Scientific Activism: Voting to Speed Up Discovery with Preprint Publishing

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By: Thaddeus Davenport, PhD

Source: Public Library of Science, via Wikimedia

         The election of Donald Trump to the Oval Office and the early actions of his administration have sparked a wave of protests in support of women’s rights and immigration, among other issues. Like other citizens, scientists have some cause to be concerned about the administration’s early actions that reveal a general disregard for facts and scientific evidence. In response, organizers have planned the March for Science for this Saturday, April 22nd, as an opportunity for people to gather in cities around the world to voice their support for factual information and scientific research. And while it is important to denounce the actions of the Trump administration that are harmful to science and health, it may be even more critical to acknowledge the underlying partisan divisions that created a niche for his rhetoric and to begin the difficult work of bridging the divide. For example, a Pew Research Center poll from 2015 indicates that 89% of liberal Democrats believe government investment in basic science pays off in the long-run, while only 61% of conservative Republicans feel the same way. Additionally, American adults with less knowledge of scientific topics are more likely to believe that government funding of basic science does not pay off. This suggests that improved science education and outreach will be important in building public support for scientific research. However, scientists often lead very busy lives and have little time outside of their professional activities to devote to valuable pursuits like science outreach. How, then, might scientists work towards building a better relationship with the public?

The products of science – knowledge, medicines, technology – are the clearest evidence of the value of research, and they are the best arguments for continued research funding. Efficiency in science is good not only for scientists hoping to make a name for themselves, but also for the public, who as the primary benefactors of academic research, must benefit from the products of that research. If taxpayers’ demand for scientific inquiry dissipates because of a perceived poor return on their investment, then the government, which supposedly represents these taxpayers, will limit its investment in science. Therefore, in addition to communicating science more clearly to the public, scientists and funding agencies should ensure that science is working efficiently and working for the public.

Information is the primary output of research, and it is arguably the most essential input for innovation. Not all research will lead to a new product that benefits the public, but most research will yield a publication that may be useful to other scientists. Science journals play a critical role in coordinating peer review and disseminating new research findings, and as the primary gatekeepers to this information, they are in the difficult position of balancing accessibility to the content of their journals with the viability of their business. This position deserves some sympathy in the case of journals published by scientific societies, which are typically non-profit organizations that perform valuable functions including scientific outreach, education and lobbying. However, for-profit journals are less justified in making a significant profit out of restricting access to information that was, in most cases, obtained through publicly-funded research.

Restricting access to information gathered in the course of research risks obscuring the value of research to a public that is already skeptical about investing in basic science, and it slows down and increases the cost of innovation. In light of this, there is growing pressure on publishers to provide options for open-access publishing. In 2008, the National Institutes of Health adopted a public access policy, which requires that “investigators funded by the NIH submit or have submitted for them to the National Library of Medicine’s PubMed Central an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication: Provided, that the NIH shall implement the public access policy in a manner consistent with copyright law.” This policy was extended through an executive order from the Obama Administration in 2013 to include all federal agencies with research budgets greater than $100 million, with additional requirements to improve accessibility.

These requirements are changing scientific publishing and will improve access to information, but they remain limited relative to the demand for access, as evidenced by the existence of paper pirating websites, and the success of open access journals like PLoS and eLife.  Additionally, other funding agencies like the Bill and Melinda Gates Foundation and the Wellcome Trust have imposed even more stringent requirements for open access. Indeed, researchers will find a spectrum of open-access policies among the available journals, with the most rapid access to information allowed by so-called ‘preprint’ publishers like biorxiv.org. Given that many research manuscripts require months or years of revision and re-revision during submission to (usually multiple) journals, preprint servers accelerate the dissemination of information that is potentially valuable for innovation, by allowing researchers to post manuscripts prior to acceptance in a peer-reviewed journal. Many journals have now adopted explicit policies for handling manuscripts that have been previously submitted to bioRxiv, with many of them treating these manuscripts favorably.

Given that most journals accept manuscripts that have been previously published on bioRxiv, and some journals even look to bioRxiv for content, there is little incentive to submit to journals without also submitting to bioRxiv. If the goal is, as stated above, to improve the transparency and the efficiency of research in order to make science work for the public, then scientists should take every opportunity to make their data as accessible as possible, and as quickly as possible. Similarly, funding agencies should continue to push for increased access by validating preprint publications as acceptable evidence of productivity in progress reports and grant applications, and incentivizing grant recipients to simultaneously submit manuscripts to preprint servers and peer-reviewed journals. Scientists have many options when they publish, and by voting for good open-access practices with their manuscripts, they have the opportunity to guide the direction of the future of scientific publishing. These small, but important, actions may improve the vitality of research and increase the rate at which discoveries tangibly benefit taxpayers, and, in combination with science outreach and education, may ultimately strengthen the relationship between scientists and the public.

March for Science this Saturday, if it feels like the right thing to do, and then strive to make science work better for everyone by sharing the fruits of research.

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Written by sciencepolicyforall

April 20, 2017 at 11:44 am

Healthcare Policy – What’s in Store for Our Future Healthcare Needs?

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By: Emily Petrus, PhD

       There’s no question that the US spends too much on healthcare – in 2015 it cost 18% of its GDP, equivalent to $3.2 trillion dollars. In fact, we spend more on healthcare to cover just 34% of our population via Medicare and Medicaid than other countries who cover their entire population with universal healthcare. Most people assume that this higher spending equals better health, but unfortunately this isn’t the case.

According to a 2015 Commonwealth Fund survey, the US has the highest infant mortality and obesity rates and the lowest life expectancy of the top 13 Organisation for Economic Co-operation and Development (OECD) countries. In addition, we have the highest rates of prescription drug use, amputation due to diabetes mismanagement, and the second highest death rate from ischemic heart disease. Our relatively small percentage (14.1%) of people over age 65 also have the highest rate of at least two chronic illnesses per person. These numbers are estimated to increase as baby boomers age, so the outlook isn’t good when considering how many elderly people we can expect to suffer from chronic health issues.

However, it’s not all doom and gloom – we are in the top 3rd for surviving cancer, boast the lowest smoking rates, and have the highest access to diagnostic imaging services (such as MRI and CT scans). In this light, it makes sense that we spend more, have better access to expensive technology, and use more expensive prescription drugs. Another way to slice the data paints a different picture. The sickest 5% of the population accounts for 50% of medical spending, and accounts for 60% of spending on prescription drugs. Together these data indicate that the US could be in better shape if we had a healthier population.

How could we make the population healthier? Let’s consider that the determinants for health are 30% genetics, 70% behavior, environment and social factors, only 10% is mediated by healthcare. Other OECD countries spend significantly more on social services such as supportive housing, employment programs, retirement and disability programs. Social services are especially beneficial for people in lower income brackets, who incidentally have the poorest health in the US. The life expectancy for the poorest Americans is about 13 years less than the wealthiest. Racial disparities also contribute to gaps in healthcare outcomes for Black, Hispanic, Asian and American Indians/Alaskan Native Americans, all of whom experience worse medical care. The parameters measured included access to care, effective communication with medical staff, and a specific source of ongoing medical care, such as a primary care physician. It is estimated that these disparities amount to billions of dollars in economic loss – $35 billion in excess health care expenditures – for example, a trip to the emergency room for something that could be treated by better access to a primary care physician. Expanding Medicaid would increase medical access to poor and disadvantaged minority groups, for example, Blacks in the south. However, many states thatch have high at-risk populations decided not to expand Medicaid. Spending more on social services aimed at improving people’s health seems to be working in other OECD countries, and the National Academy of Medicine recommends the US increase spending in these areas.

Social services are unlikely to gain support from conservatives, so spending in this area is unlikely to be supported by the current administration. However, there are other areas in healthcare that can gain bipartisan support. 30% of medical expenses are considered wasteful – meaning they are for unnecessary services, fraud, and sky high pharmaceutical or administrative costs. Medicare has already saved billions of dollars by reducing overpayments to private insurers and tying medical provider payments to quality of care. Overall a goal of those involved in healthcare reform should seek to follow this example of prioritizing value over volume of care, which will translate to better outcomes at lower costs for patients and taxpayers.

So what did the Affordable Care Act (ACA, also known as Obamacare) achieve since it was passed in 2010? In the time leading up to the ACA, 82% of the American public wanted healthcare reform. Private insurance premiums were rising 10% per year, and insurance didn’t have to cover expensive benefits, so many plans came without services like mental health or maternity care. Maternity care is not just a women’s issue, healthier pregnancies result in healthier babies who become part of our population. Before the ACA, 50 million (17%) of the population was uninsured; by 2016 20 million people had gained health insurance, leaving only 10% of our population uninsured. Women and people with pre-existing conditions can’t be denied coverage or charged more by insurance companies. Lifetime spending caps were removed, meaning if you were a sick baby in the ICU you can’t be denied coverage for the remainder of your life. The most popular part of the bill allows young adults to stay on their parents’ insurance until age 26, which reduced the uninsured rate for young adults by 47%. Finally, tax credits made health insurance through exchanges more affordable for those at or below 400% of the federal poverty line.

Those are the good parts about the ACA – here’s the bad news.  High deductible plans have increased from 10% of plans offered in 2010 to 51% of plans in 2016, meaning people buying insurance can expect to pay at least the first $1,000 per year out of pocket. If it seems that premiums are jumping, they are: they rose 20% from 2011 to 2016. It’s easy to blame the ACA for rising premiums, but if we consider that premiums rose 10% per year before the ACA, 20% in 5 years doesn’t sound so bad. Some specific states are expecting huge increases, for example Oklahoma will see a 42% increase in 2016. Part of the reason premiums are rising is because healthcare gets more expensive each year – it outpaces inflation and wages. Insurance companies are also losing money because they have enrolled more sick, expensive people than they expected to when they set prices. The ACA attempted to mediate the sticker shock for insurance companies by setting up “risk corridors” to help shoulder the burden, but that part of the bill was scuttled for political reasons, and now insurance companies are passing the buck to consumers. Regarding taxes, under the ACA, those without insurance will face a penalty fee double that of the 2015 amounts.

A central campaign promise of Trump and Republicans was to repeal the ACA and provide better and more affordable coverage for all.  The American Health Care Act (AHCA) proposed several weeks ago by Republicans was a repeal and replace bill which was unpopular from the start. The AHCA was unpopular with conservatives for not going far enough to repeal the ACA, while moderates worried about the 20 million people, including their constituents, being denied or outpriced from insurance due to some elements of the bill. The AHCA removed the mandates requiring insurance companies to provide essential health benefits. This could lower premiums but insurers could also reduce services, leading to “junk plans”. Additionally, tax credits for people buying insurance would be significantly lower than current levels, making insurance too expensive for many middle-income people. Medicaid coverage was also proposed to shrink, resulting in less coverage for poor Americans. Finally, eliminating the community rating of the ACA would enable insurance companies to charge older and sicker people higher premiums, essentially pricing those who need insurance the most out of the market. The AHCA proposed to ameliorate this problem by providing larger tax credits to older individuals and setting up pools of high risk people subsidized by the government.

It is safe to assume that the Republican controlled House, Senate and the White House will try again to present bills that modify the ACA. However, it remains to be seen if they will try a bipartisan effort to fix certain parts of the bill that are flawed, or repeal and replace the ACA with something completely new.

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Written by sciencepolicyforall

April 14, 2017 at 9:22 am

The Trans-Pacific Partnership and its Impact on Pharmaceutical Affordability

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By: Shakira M. Nelson, PhD, MPH

        For many, the Trans-Pacific Partnership (TPP) was a point of great debate during the 2016 Presidential primaries and election. As a simplified explanation, the TPP is a free-trade agreement involving the United States, Canada, Australia, Japan, New Zealand, Mexico, Chile, Peru, Brunei, Malaysia, Singapore and Vietnam, intended to “level the trading playing field” through the elimination of tariffs and other laws that create trade barriers. In its final form, the TPP would impact up to one-third of world trade and 40% of the global gross domestic product. Many who debated the ramifications of the TPP did so in the context of foreign policy interests. Although aligned with foreign policy, a major part of the TPP deals with intellectual property protection, and pharmaceutical drug development. If implemented, the effects of the TPP could greatly diminish public access to affordable medicines, both domestically and internationally. Moreover, the stronghold the TPP places on intellectual property could limit the development and marketing of less expensive options.

Intellectual property can be divided into two categories: industrial property and copyright. Patents, trademarks, and industrial design fall under industrial property. Patent development is a large part of scientists’ work, seen as almost a necessity to incentivizing innovation. Many argue that, without the ability to patent inventions and significant findings, scientists would not be able to generate profits used to sustain research and development; within the pharmaceutical industry, patents are the proverbial bread-and-butter. When in place, patents create a stronghold around the release of new chemical drugs, which prevents competition by generic brands. The standard length of time of a patent for a chemical drug is 20 years, which starts from the time the drug is invented.

Many new medicines under development today fall under the category of ‘biologics’. As the name suggests, biologics are treatments made from biological sources, and are very different from chemical drugs. Created to treat a multitude of diseases, including Ebola and cancer, biological sources include vaccines, anti-toxins, proteins, and monoclonal antibodies. Given their structural complexity compared to traditional drugs, and use of recombinant DNA technology, biologics are more difficult, and costlier to make. Moreover, manufacturers have a greater burden in ensuring product consistency, quality, and purity over time. This is done through certifying that the manufacturing process remains the same over time. Because of this, it is estimated that the price to manufacture biologics cost on average more than 22 times the price of chemical drugs. Current laws state that generic biologic development, known as biosimilars, cannot be approved until 12 years after the branded product has been approved – this is known as an exclusivity period. This was enacted under the Biologics Price Competition and Innovation Act of 2009, by the Food & Drug Administration (FDA).

The challenge with current policies is establishing a period-of-time that balances the need for companies to generate profits and cash flows, which will incentive them to conduct more research and compensate them for the extensive manufacturing processes, with the need to provide greater access through launching generic drugs and biosimilars. The trouble with the proposed policies of the TPP agreement is that they seem to embolden the pharmaceutical companies by introducing changes that would prevent competition from generics and biosimilars for longer periods of time than the current basic terms. The implications of this are far-reaching, as it may lead to a significant increase in the current costs of pharmaceutical drugs and biologics, hindering the health of the patients who rely upon these treatments.

Critics of the current system of patent length and biologic exclusivity periods fear that rather than incentivizing innovation, companies are being rewarded through their ability to charge higher amounts for drugs without the fear of competition on the market. Health policy experts concur, identifying policies such as the Hatch-Waxman Act of 1984 in allowing for the creation of drug monopolies, and “going too far in compensating the pharmaceutical industry at the public’s expense”. A report released in 2009 by the Federal Trade Commission stated that biosimilar development was more difficult to achieve than traditional generic drugs. For example, development requires comparisons to the original biologic, to prove efficacy and equivalence. Biosimilars must share the same mechanism of action, with no clinically significant differences in terms of safety or potency for the approved condition of use. The steps necessary to achieve this are significant, and therefore imposing a 12-year exclusivity period on biologics may be unnecessary. US Congressmen have pushed to compromise, floating an amendment to the TPP that would lower the exclusivity period to 8 years. However, critics and patients who rely upon drug competition to lower market prices, have protested this amendment stating that costs of new drugs and biologics are too high, and 8 years is too long of a length of time to wait for affordable generics and biosimilars to come on to the market.

The impact of decreasing the length of time it takes for biosimilars to come onto the market can be seen with Neupogen, a leukemia drug that was first approved by the FDA in 1991. Delivered via injection, Neupogen costs patients $3,000 for 10 injections. With injections needed daily, this drug could carry a price tag of well over $100,000 per year. It wasn’t until recently, however, that the first biosimilar was approved on the US market. The biosimilar, Zarxio, was approved as a leukemia drug and is priced at more than $1000 less than Neupogen. This pricing has the potential to decrease the yearly costs of this drug from $100,000 with Neupogen to $55,000-$75,000. Further evidence of these financial savings was provided by the Rand Corporation, which predicted a savings of over $44 billion over 10 years with an increased approval of biosimilars, for patients who rely upon these specific cancer treatments.

Internationally, the policies of the TPP also have far reaching effects on the availability and costs of pharmaceuticals. The 12-year exclusivity period would be imposed upon the other countries involved in the TPP, where currently for some, such as Brunei, there is no current exclusivity protection. By imposing the 12-year period, global competition could become restricted. Additionally, the TPP proposes other key patent protections that play a bigger role on the international market. One protection, known as evergreening, allows drug companies to request patent extensions for new uses of old drugs. The immediate effect of this is an extension of monopolies on drug sales for minor reasons. The second protection allows pharmaceutical companies to request patent extensions if it takes “more than 5 years for an application to be granted or rejected.” Advocacy groups fear that the price of drugs would undermine the efforts of health initiatives, such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria. These initiatives rely upon price competition to manage costs, with the availability of cheap generics helping drive costs down.

Although the current administration has ended the USA’s association with the Trans-Pacific Partnership, it is important to note that other countries may try to implement some of the policies, affecting the availability and affordability of drug treatments. To decrease this burden, the US could work to assist in negotiating exceptions for the poorer and smaller countries, to help them meet any challenges they may come up against. Within the US itself, it is important for policies, laws and any future trade agreements to be modified, with more of a focus on the affordability and regulation of drugs and biologics. Imposing price controls may offer a modest benefit, but may not be a long-term solution. A focus on lowering the patent length for new drugs and biologics can be an immediate step. Although the push back from pharmaceutical lobbyists will be substantial, alleviating the financial burden on families afflicted with cancer and diseases should be the focus.

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How to Make a Valuable Postdoctoral Experience: Updating the Model

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By: Aparna Kishor, MD, PhD

       To an outside observer, the scientific enterprise in the US appears to be thriving. The 2016 budget of the National Institutes of Health (NIH) was $31.3 billion. Of this, about 80% was distributed to research projects performed extramurally, pointing to the fact that hundreds of thousands of researchers nationwide, established scientists as well as trainees, benefit from the funding. Although the numbers are somewhat murky, it is likely that over 50% of graduate students and postdoctoral researchers (postdocs) receive some federal funds.

A more granular view of the reality of modern scientific training reveals its true complexity. In The Postdoctoral Experience Revisited, a report on postdoctoral training in the US, the National Academies argue that there are serious issues in the way we train our young scientists today, including those having to do with recognition and compensation, mentorship, and career advising. Fundamentally, although the US has more postdocs than ever before, does this serve the individuals involved?

First some context. For those committed to a career in the biological sciences, the first stage of training is graduate study to acquire technical and field-specific skills, culminating in a PhD. Traditionally, the second is the postdoctoral stage, which provides additional technical experience and preparation for a future career, ideally culminating in a research position. In the US, approximately 65% of those with graduate degrees in the life sciences continue on to a postdoc which is the field with the highest rate of entry. The second highest is in the physical sciences, with only 50%. Although the quotidian experiences of the two may be similar, the graduate and postdoctoral stages are actually quite different, particularly since graduate training tends to have formal requirements and expectations while postdoctoral training, does not. This framework also has distinct benefits for the principle investigators (PIs). A major one is economic: junior scientists are a willing, and in the case of postdocs, highly trained, source of cheap labor (more on this below). On occasion, the work may be done at no cost to the PI if the trainee has funding from another source, although this is becoming proportionally less common.

When the postdoctoral arrangement was established in the early part of the 20th century, the training periods were typically 1-2 year stints in a lab to learn additional skills and consolidate connections in the field. After this, the young researcher would generally transition into an academic position. In the 1970’s, close to 55% of postdocs held tenure or tenure track faculty positions 6 years after completion of their graduate studies. Now, when a postdoc plans for his or her next career move, the situation is not so simple and this has aroused the concern of the National Academies. Partly, the difficulty is due to the number of available academic positions being outstripped by the number of postdocs in the pipeline. Data from 2006 show that only 33% of postdocs had faculty positions 6 years after graduate school and only half of those were tenured or tenure-track. The rest of the explanation lies in the fact that the landscape of the scientific enterprise has evolved.

Most obviously, the demographics of the postdoc community are markedly different from those in the early 20th century resulting in different needs for trainees. As of 2014, women were receiving close to 50% of all life science doctorates awarded in the US. Gender parity at graduation has not carried through to the faculty level (where only approximately 25% of tenured faculty are women). Among the many potential causes for this decline, one is that many women leave the academic track due to the challenges in balancing a career with raising a family. Nonetheless, there are more women at all levels in the sciences than before, indicating that retention may be increased by supporting women during the time that their children are young. Holders of temporary visas comprise another important population, but there are very few concrete data pertaining to them. They obtain close to 25% of all doctorates in the biological sciences, and 80% of those who have jobs after graduation stay in the US. With this, there is significant flux into the system at the postdoc level. As a result, upwards of a third of all biomedical postdocs in the US are foreign nationals primarily from India and China. Since these people have never been counted, the best way to help them meet their goals and the role they play in the US scientific arena are undefined.

Another important change is that postdoctoral training periods have lengthened from 1-2 years to around 4 years. For those who want the training, this timeline extension is believed to be a necessary sacrifice in order to gain entry into the competitive world of academia. Unsurprisingly, the percentage of PIs under 36 has fallen from 18% from 1980 to 3% in 2010. For established investigators, the longer training times are advantageous. Postdoc salaries at research institutions generally amount to less than the combined tuition-plus-stipend package offered to graduate students. After a few years, a postdoc may conduct research at a level equivalent to that of permanent scientific staff but at a fraction of the cost – postdocs pull in anywhere from $40,000 to $49,000 a year, while staff will have full benefits and a salary closer to $80,000 a year. Given this, the challenge is to make a prolonged training period valuable, feasible, and non-exploitative for all who choose it.

Finally, there is growing evidence that a postdoc may not be the right choice for everyone. Most junior scientists feel limited by the now-classic dichotomy between pursuing research in academia and industry. The reality is that many other career options exist, although some are a step or two removed from pure research. These are in areas like consulting, intellectual property, and science policy. Some jobs will provide entry-level incomes greater than a postdoc, and may even lead to career prospects that are more secure than that in research. Entry level salaries for some careers in industry begin at $70,000 and mean salaries in industry can be $40,000 more than that in academia, and the age at first non-academic job is lower than that for academics. Critically, for those wishing to optimize some of these other aspects of their professional advancement, a postdoc may be unnecessary.

Taken together, these developments indicate a need to change the culture surrounding the postdoc. The essence of the National Academies’ recommendation to improve the postdoctoral experience is that the entire scientific community must treat it as a valuable training opportunity instead of basic employment. To this end, the minimum postdoctoral salary should be increased, even beyond the current $47,484.  The improved economics for trainees will have a number of benefits: it will place more value on these individuals, limit the number of postdocs an investigator may hire, perhaps encourage more women to stay in research, and make positions more competitive, lessening their use as a default employment option. Postdocs should also be encouraged to receive individual funds as proof of independence. There is some evidence that postdocs on their own fellowships are more satisfied than those funded by their lab, although it seems likely that people more committed to a career as a researcher are the ones most likely to apply for fellowships. Additionally, those who receive early career grants are more likely to receive independent investigator grants and faculty appointments. Finally, there is an argument for more staff positions as a measure to keep postdoctoral opportunities as dedicated training experiences.

For now, it is important for each researcher to decide whether it is in his or her best interest to embark on the postdoctoral route. Fortunately, career advising is increasingly available to trainees at all levels and the NIH and other groups have issued mentorship guidelines for postdocs. Overall, the entire scientific community must assist in returning value to a postdoc and in meaningful career development for all trainees.

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Written by sciencepolicyforall

March 10, 2017 at 9:56 am

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

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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.

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Written by sciencepolicyforall

March 3, 2017 at 9:21 am

Synthetic Biology to Cure Diseases – Promises and Challenges

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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.

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Written by sciencepolicyforall

February 23, 2017 at 4:33 pm