Advancing biological therapies against a rising tide of American anti-science and other external threats

KEYWORDS:

• Funding
• anti-vaccine
• research and development
• NIH

1. Introduction

Since the beginning of this new millennium, we have seen dramatic improvements in global public health by providing access to new health technologies. This observation is especially true for vaccines and other biologics. For example through Gavi, the Vaccine Alliance, today an unprecedented number of children receive access to life-saving vaccines, including two new vaccines to prevent rotavirus and pneumococcal disease, respectively. Similarly, global populations now have increasing access to vaccines for the prevention cervical cancer (human papillomavirus) and liver cancer (hepatitis B) in adults. The health impact of these vaccines has been recently measured by the Global Burden of Disease Study 2016, which reported recently on the substantial reductions over the past decade in childhood deaths from vaccine-preventable diseases, as well as deaths from infection-related cancers [1]. Beyond vaccines, we’re also starting to see the benefits of new monoclonal antibody therapies now being used to treat cancers and autoimmune illnesses, while through the pioneering work of Allan Goldstein and his colleagues, new biologics such as thymosin β4 are finding increasing uses for a wide spectrum of non-communicable diseases (NCDs) [2].

2. New research and development technologies

These victories could be just beginning as an array of upstream technologies is making it possible to develop new-generation vaccines and biological therapies. They include expanded use of model organisms such as Caenorhabditis elegans, single-cell combinatorial indexing RNA sequencing (sci-RNA-seq), functional and comparative OMICS, CRISPR/Cas genome disruption and editing, artificial intelligence and machine learning, and systems biology and immunology, just to name a few [3]. Recently, sci-RNA-seq has been linked to precision and personalized medicine to tailor new and innovative treatments for human disease [4], which could represent a breakthrough in precision approaches for developing human biologics.

Therefore at one level, we have everything in place to ensure rapid progress in translational research and development (R&D) as it pertains to biological therapies. We have created organizations such as Gavi, the Vaccine Alliance, to maximize global access, while simultaneously implementing upstream biotechnologies to refresh and populate a new pipeline of cutting-edge interventions. In so doing, we are positioned to simultaneously address NCDs, pandemic infectious disease threats, and now even some of the chronic and debilitating neglected tropical disease [5].

However, there are also forces in play that could undermine our current successes and dramatically reverse our gains. Sadly, most of our challenges are non-scientific, and in some cases, they represent ‘self-inflicted wounds’ (Figure 1).

Figure 1. The ‘Yin and Yang’ of vaccines and biologics.

3. Challenges and obstacles

Today, one of our most formidable challenges is lack of funding. Our US National Institutes of Health (NIH) has an annual budget of $32 billion [6], although some projections suggest that this number might increase soon to $34 billion. Overall, however, these dollar amounts have increased only very modestly since 2003, when the NIH budget was around $26 billion, such that over the last 15 years, the NIH budget has increased only around $0.4 billion or 1.5% annually. For all practical purposes, these numbers indicate that the NIH budget has been mostly flat for almost two decades. Federation of American Societies for Experimental Biology estimates that our lead agency for supporting biomedical research has lost more than 20% of its ‘capacity to fund research due to budget cuts, sequestration, and inflationary losses’ [7].

A potentially grave consequence of shortfalls in federal biomedical R&D funding is its impact on young and midcareer investigators who are disproportionately suffering from lack of funding and in many cases leaving academic scientific careers. By not specifically targeting substantial NIH and other grants for young scientists, we need to be concerned that America will no longer lead innovation for new biological therapies. This trend is in contrast to several other countries such as China, Germany, and Singapore where R&D investments continue to accelerate. China in particular has been aggressive in its investments in both R&D and doctoral education and could possibly overtake either the US or the European Union in these categories coming years [8]. Such trends together with China’s new global outreach through a so-called ‘Belts and Road’ Initiative for Africa, Asia, and elsewhere may portend a shift in biologics innovation from the United States to China.

Equally concerning is the steep rise in anti-science sentiments in America. While climate denial and the US exit from the Paris climate accords are often cited as evidence of a US retreat from science, with respect to biologics perhaps the most tangible evidence is the abrupt ascendancy of the American anti-vaccine movement [9]. In 2015, a serious measles outbreak in California made US public officials aware of the dangerous consequence of allowing non-medical exemptions for reasons other than religion. They are sometimes referred to as ‘philosophical belief’ exemptions [9,10]. Although the California legislature subsequently closed off this option, there remain almost 20 US states that still allow these vaccine exemptions [9]. Since the 2000s, we have seen significant increases in non-medical exemptions in these states such that we have created national hotspots in US cities where there are hundreds or even thousands of school-aged children not receiving their vaccines. For example, the rise is striking in the state of Texas where there has been a massive wave of non-medical exemptions since 2003, to the point where there are more than 50,000 school-aged children not getting vaccinated [9,10]. And this number does not take into account home-schooled children. In many ways, Texas has become an epicenter of the American anti-vaccine movement for reasons that are still under investigation, but they include the fact that several of the global leaders who led the launch of this movement at the start of the new Millennium now reside in Texas, together with the fact that an organized and well-funded political action committee was created in the state [10,11].

Of particular concern in Texas and the other non-medical exemption states is the potential re-emergence of the disease, measles, due to its high transmissibility and its historical ability to cause disease outbreaks once vaccine coverage rates begin to decline [12,13]. Besides California, in 2017, a large measles outbreak erupted in Minnesota due to an abrupt decrease in vaccination rates among an African immigrant community where anti-vaccine activists worked to aggressively spread phony information about vaccines [14]. It should be noted that measles epidemics also spread across Europe in 2017 and into 2018. There are further concerns that American (and European) anti-vaccine attitudes are creating an anti-science culture that could spread to other nations, including low- and middle-income countries, with the risk that our important twenty-first-century global public health gains might be lost [15]. In response to rising anti-vaccine activities in America, this author has undertaken efforts to lead a pro-vaccine countermovement (based on his role as both vaccine scientist and autism parent), which systematically refutes claims that vaccines cause autism and other alleged chronic conditions [16,17].

4. Fighting back

The rise of American anti-science did not occur in isolation. Instead, flat-line NIH budgets and an aggressive antivax movement flourish in an enabled environment due to a number of factors, including (as some allege) a lack of strong science proponency in the US Congress, as well as the White House and the Department of Health and Human Services. However, there is also a concern that the scientific community itself has been all too silent in advocating for R&D. The policy group Research!America for instance finds that more than 80% of Americans cannot name a living scientist [18], while the Pew Research Center finds that fewer than one-half of scientists ever blog about their research or discuss it on social media [19].

There are several important American science and advocacy initiatives currently in place, which could address some of these concerns. They include an important Science and Technology Fellowship supported by American Academy for the Advancement of Science [20] and a new initiative on the public face of science from the American Academy of Arts and Sciences, with an emphasis on public engagement [21]. Beyond these activities, this author has proposed a more comprehensive program of public engagement led by working scientists. Known as Science Tikkun, this approach synthesizes modern science with an ancient Jewish philosophy of tikkun olam (‘to repair the world’), which reached its full expression in sixteenth-century writings from the Kabbalah [22]. Science Tikkun attempts to reverse traditional norms of science focused only on grants and papers and writing only for other scientists, in order to insist on public outreach as a necessary and vital scientific activity [22]. By speaking out and addressing public and lay audiences, the science of vaccines (vaccinology) and biological therapeutics could become better integrated into modern society and in the US seen as an important and necessary activity.

A good example is the rise of the American anti-vaccine movement, which has now resulted in widespread declines in vaccine coverage in Texas and now 17 other states allowing personal belief exemptions [23]. In these states and elsewhere, there is a disproportionate impact on the uptake of newer vaccines such as the cervical cancer vaccine to prevent human papillomavirus infection [24,25]. Similar sentiments could slow or halt the introduction of additional new vaccines, such as a new herpes zoster vaccine [26] or even next-generation biologics. Science Tikkun is proposed as a mission critical activity to ensure global access to essential vaccines and biologics.

During an era of heroic science over the past few decades, we made tremendous progress on the R&D and delivery of an array of exciting vaccines and biological therapies. We built vaccines to conquer ancient childhood afflictions and infection-related cancers. Now, biological therapies are addressing a vast array of NCDs. It’s important that this legacy does not go to waste.

Declaration of interest

The author is patent holder on vaccines against schistosomiasis and hookworm which are in clinical trials. The authors have no releva nt affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded. Part of the content of this paper was presented at Fifth International Symposium on Thymosins in Health and Disease and is part of a supplement issue funded by SciClone Pharmaceuticals.