Phages for Global Health

Dr. Tobi Nagel is Founder and President of Phages for Global Health, a non-profit facilitating the application of antibacterial phages to combat antibiotic resistance in developing countries. Tobi spent 15 years in the pharmaceutical industry co-developing drugs that have been tested in >80 clinical trials. She was a Moonshot Fellow of the Kravis Lab for Social Impact, a Fulbright Specialist roster member, an Advisor to Phages for Human Applications Group Europe, a Scientific Consultant for Global Strategies for HIV Prevention and CRDF Global, and a founding Editorial Board member of the scientific journal PHAGE. She is currently an Advisory Board member for both the Phagebiotics Research Foundation and PhagePro, a company developing cholera phages. Tobi did a Postdoctoral Fellowship at the American Hospital in Turkey and completed a PhD in Medical Engineering at the Harvard-MIT Division of Health Sciences and Technology and a BS in Chemical Engineering at Stanford University.

A 2014 report predicted that by 2050 approximately 10 million people will die each year from antibiotic-resistant infections -- equivalent to >10 times the annualized death rate from coronavirus. Inappropriate use of antibiotics in COVID-19 patients is expected to accelerate antibiotic resistance rates further. Thus, we urgently need antibiotic alternatives, particularly in Africa and Asia, where 90% of the antibiotic-resistant deaths will occur.

Before antibiotics were discovered, bacteriophages (AKA phages) were utilized as antibacterial agents. Phages are viruses that exist in the environment and our bodies that can kill antibiotic-resistant bacteria. Phage-based drugs are now regaining popularity in industrialized countries, but few researchers in developing countries know anything about them. We are filling that gap by teaching developing world scientists how to isolate phages, then partnering with them to develop phage products locally. By empowering these scientists, we aim to drastically decrease the number of lives lost to antibiotic resistance.

We are addressing the global antibiotic resistance problem, which is expected to cause 10 million deaths each year by 2050 -- far more than the >500,000 deaths that COVID-19 has caused worldwide during the first 6 months of that pandemic. Unfortunately, almost 90% of the deaths from antibiotic resistance will occur in developing countries in Africa and Asia. Misuse of antibiotics in livestock, food crops and people has accelerated development of resistance worldwide. To compound the problem further, no new antibiotics have been introduced in over 30 years; all recent antibiotics are simply variations in existing drug classes. Also, drug companies consider antibiotics too costly to develop for so-called “bottom of the pyramid” populations in the developing world. Without new types of drugs to combat infections, the World Health Organization warned in 2014 that a post-antibiotic era -- in which routine infections can once again become life threatening -- is “far from being an apocalyptic fantasy, [but] is instead a very real possibility for the 21st century”.

Phages for Global Health works in developing countries to facilitate the application of phages, which are inexpensive, naturally-occurring antimicrobial agents that can kill antibiotic-resistant bacteria. Phages have been used successfully against problem bacteria for >100 years in certain parts of the world, particularly in the former Soviet Union, and organizations such as the Gates Foundation and the US National Institutes of Health have regarded phages as a key technology to combat the antibiotic resistance crisis. However, no phage products are yet available in developing countries, and few scientists there have any knowledge about the potential benefits of phages.

We are bridging this gap through 2 broad approaches: 

1. Teaching scientists how to develop phage products (through a series of hands-on laboratory workshops in Africa and Asia)

2. Creating international teams of global phage experts and developing world scientists to co-develop phage products (e.g., for poultry meat decontamination, cholera prevention, treatment of tuberculosis, etc)

We are reaching two different levels of target populations: first, public health scientists in developing countries and, second, the communities they serve. Our primary goal is to provide scientists a tool (phages) to help combat the antibiotic resistance crises in their countries. By partnering with them through trainings and collaborations, we aim to empower these scientists to develop products that are both technically effective and socially accepted within their local cultures. 

In July 2017 we began delivering regional laboratory training workshops: three in East Africa, one in West Africa, and our first workshop in Southeast Asia was scheduled for November 2020 (postponed due to coronavirus). The latest surveys of the workshop participants indicate that for each scientist we have taught, they have trained at least 15 others through their home institutions -- meaning that over 1100 African scientists have been introduced to phage biology in the past three years. The workshop participants have also initiated more than 50 new phage development projects and have won grants totaling to over $850,000. Given this rapid amplification of efforts, within the next few years the products developed by these scientists could potentially save many thousands of lives, if not more.

During my career in the pharmaceutical industry I also consulted on the side in developing countries. The juxtaposition of working in those two worlds was often disconcerting: I was making drugs in the US that typically cost 1 billion dollars to develop, yet most people whom I met in the developing world would never be able to access those drugs. So I spent a number of years looking for ways that I might be able to apply my skills to address diseases in developing countries. In June 2013 I helped teach a short-term workshop in the country of Georgia, where phages have been a standard component of medical practice for decades, including as over-the-counter drugs. Several of the participants in that workshop were from the world famous Eliava Institute, the leading phage research center in the former Soviet Union. I remember the moment one of my Georgian colleagues gave a presentation about her phage research, and I instantly realized this was the type of drug technology I had been looking for -- one that was both effective and affordable. It took another 6-12 months for the ideas to fully germinate, then I eventually founded Phages for Global Health.

I am frustrated that our current drug development system -- which ideally should be a public benefit system focused on healing people and saving lives -- is instead driven primarily by profit incentives. In our current system, drugs almost never get made unless there is a clear path for financial gain. And the stark outcome is that people die unnecessarily, largely because they were born in the wrong part of the world. Even though I experienced career success in the traditional drug development field, I became disheartened by the fact that companies often do not develop drugs that could save thousands of lives -- simply because those people cannot pay. So I am now applying the skills I gained in the pharmaceutical industry toward one of the greatest medical needs on the planet. And I get a surprising amount of satisfaction and joy from bringing together scientists with a similar hunger for serving the people in their own countries.

There are few people who have both drug development expertise and experience working in developing countries -- since a career in the pharmaceutical industry usually occurs in industrialized countries. My unconventional career path has enabled me to develop this unusual combination of skills. 

I chose to do a Postdoctoral Fellowship at the American Hospital in Istanbul -- studying patients with a rare bleeding disorder -- even though I had other offers for traditional jobs in the US. That Fellowship served as a crash course not only in how to learn about other cultures, but also in how to conduct laboratory research in suboptimal settings, such as when the electrical power fluctuated or there was little clean water available. My aptitude for and love of working in those types of settings has persisted and grown ever since.

I bring to my work a knack for building networks cross-culturally, enabled by a collaborative leadership style and strong interpersonal skills. I also bring drug development expertise to the phage research field, and I was recently asked by the US National Institutes of Health to serve as a grant reviewer for phage therapy proposals from around the world. In addition, I am able to combine long-term strategy development with short-term tactical planning. Perhaps most importantly, I have always been deeply motivated to save lives through my drug development work. Through Phages for Global Health I am now able to amplify those efforts by empowering others to save lives in their own countries.

We encountered major obstacles when planning for our first laboratory training workshop in West Africa. Our initial plan was to deliver the workshop in Nigeria during October 2018. However, a few months before the workshop, civil unrest escalated in Nigeria -- a 24-hour curfew was imposed in regions near the planned workshop site and, sadly, a relative of one of our colleagues there was killed amidst the violence. So our team decided to move the workshop to Ghana, with the new plan being to run the workshop in January 2019. Unexpectedly, student protests broke out on the university campus in Ghana where we had planned to hold the workshop. That eventually led to changes in the university's academic calendar such that we could not get full access to the teaching laboratory for several months. Nonetheless, our team persisted and our funders agreed to provide extensions for the grant expenditures, so we eventually succeeded in delivering the workshop in Ghana during July 2019.

Our board members and I joke that my title should be "Chief Persuasion Officer" instead of "Chief Executive Officer" or "President". This is because we function via a collaboration model -- working with experts around the world -- rather than through a hierarchical leadership model in which all the employees work in our own organization. To succeed, I must identify and persuade appropriate collaborators to join a project, leading in their own specialties. I serve as the overall strategic leader, drawing upon the unique expertise, cultural understanding and personality of each colleague and bridging between various scientific and business specialties. I believe this collaborative leadership style is more effective since we benefit from the strengths of each teammate and everyone actively commits to his or her role in the mission. For example, in developing a phage product to decontaminate poultry meat, I focused the work in Kenya, the country with the highest fatality rate for the specific bacteria we are targeting. I first recruited the Kenyan scientist who had gathered the largest collection of that type of bacteria, then the leading phage expert in that field (from the UK). Together, we are now developing that product for deployment in Kenya.

Most efforts to address antibiotic resistance focus on prolonging the effectiveness of existing antibiotics or financially motivating new drug innovation through the traditional drug development process. The former approach -- ensuring that antibiotics are only used when medically appropriate -- will just delay the inevitable: all current antibiotics will eventually become ineffective. And the second approach -- incentivizing pharmaceutical companies to make drugs for “third world” diseases -- is considered futile by many global health leaders because of the expense (1 drug usually costs $1 billion). We believe that phage-based drugs can provide a solution since they could be (1) developed cheaper and faster than conventional drugs, (2) designed to minimize future resistance, and (3) produced with relatively simple equipment that is readily available to developing world scientists. To our knowledge no other organization is specifically working to bring phage technology to developing countries. 

Before the coronavirus pandemic, we were on track to double the number of laboratory training workshops we deliver each year. While we now need to postpone those workshops, we do have funding in place as well as an expanded team of instructors to handle the increased workload. Thus, we will continue on our original trajectory once it is safe to deliver in-person trainings again, hopefully in 2021.

We have also begun developing the curriculum for an advanced workshop focused on the practical aspects of bringing phage products to market. It includes topics such as formulating and manufacturing phages at scale, seeking regulatory approval, developing financially sustainable models, seeking business partners, and engaging key stakeholders regarding utilization of the future products. We have identified numerous experts in these areas who are enthusiastic to deliver the workshops, likely beginning in late 2022. Our plan is to make these workshops available to scientists who have already successfully isolated phages and are therefore ready to take the next steps in developing products.

With the workshops underway and a network of in-country phage scientists expanding, my next goal is to help developing country regulatory authorities prepare to supervise phage products in their countries. I have started bringing together a team of African, European and US policymakers to draft general guidelines that developing country leaders might refer to as they begin to regulate phage products. My goal is to spend time in several countries, working face-to-face with these leaders as we draw up the guidelines.

We deliver 2-week, hands-on laboratory training workshops through which we teach scientists how to isolate and begin to develop phages as antibacterial products. For each workshop, scientists from a specific region (East Africa, West Africa or Southeast Asia) are selected through a competitive application process, with partner institutions from surrounding countries helping with publicity and selecting appropriate participants. Instructors come from leading institutions in the US and Europe.

HOST INSTITUTIONS FOR LABORATORY TRAINING WORKSHOPS:

Makerere University (Uganda) - 2017

Pwani University (Kenya) - 2018

Kwame Nkrumah University of science and technology (Ghana) - 2019

Muhimbili University of Health and Allied Sciences (Tanzania) - 2020

Asian Institute of Medicine, Science and Technology (Malaysia) - postponed from November 2020 until 2021 due to coronavirus

PARTNER INSTITUTIONS FOR LABORATORY TRAINING WORKSHOPS:

Kampala International University (Uganda)

University of Nairobi (Kenya)

Institute of Primate Research (Kenya)

Technical University of Kenya

Sokoine University of Agriculture (Tanzania)

National Health Laboratory (Tanzania)

University of Rwanda

National Veterinary Research Institute (Nigeria)

University of Lagos (Nigeria)

University of The Gambia

Primate Research Center at Bogor Agricultural University (Indonesia)

Yale University (USA)

University of Leicester (UK)

University of Warwick (UK)

Hopitaux Universitaires de Geneve (Switzerland)

We have also brought together international teams to develop phages for poultry meat contamination, cholera outbreaks, and tuberculosis treatment.

COLLABORATING INSTITUTIONS FOR PHAGE PRODUCT DEVELOPMENT:

Kenya Medical Research Institute

Ministry of Health (Democratic Republic of Congo)

Yale University (USA)

University of Nottingham (UK)

University of Leicester (UK)

University of Alberta (Canada)

Queen Astrid Military Hospital (Belgium)

As a registered 501(c)(3) non-profit organization in the US, Phages for Global Health has been able to raise approximately $750,000 through individual donations and grants from the following foundations and governmental agencies:

Bill & Melinda Gates Foundation (US)

Conservation, Food and Health Foundation (US)

Kravis Lab for Social Impact (US)

Biotechnology and Biological Sciences Research Council (UK)

Microbiology Society (UK)

The Company of Biologists (UK)

Lions Club of Maarn (Netherlands)

An anonymous foundation

We anticipate being able to raise similar levels of funding through pending and future grant proposals, as well as through ongoing crowdfunding campaigns. In addition, we have been approached by companies interested in partnering to produce some of the phage products that our international teams are currently developing. One beneficial scenario would be to generate revenue through such partnerships by selling the phage products in industrialized countries, thereby generating income that could support our ongoing non-profit training activities and future product development.