Foundation for the National Institutes of Health — Working Group on Malaria Gene Drive Testing Path

 

We decided to write about this grant in order to share the rationale for our interest in gene drives. This page is a summary of the reasoning behind our decision to recommend the grant; it was not written by the grant investigator(s).

Foundation for the National Institutes of Health staff reviewed this page prior to publication.


The Open Philanthropy Project recommended a grant of $1,228,845 to the Foundation for the National Institutes of Health (FNIH) to form a working group to support development of a consensus pathway for field testing modified mosquitoes with driving transgenes.

The FNIH proposes to convene a working group of approximately twenty experts to recommend a consensus path for field testing gene drives to fight malaria. This recommendation will include guidelines on how to safely field test gene drives for population modification and population suppression of vector mosquitoes in order to determine whether they could safely and ethically be deployed widely. To date, the FNIH and the Bill & Melinda Gates Foundation (BMGF) have been key actors supporting the development of this new technology, including commissioning of prior independent studies to consider best practices, and we think the FNIH is well positioned to convene a working group to develop a field testing pathway that can be used to inform researchers and other stakeholders. Our hope is that developing consensus around a testing pathway will clarify the requirements and reduce the amount of time needed before a gene drive affecting malarial burdens could be released, if the technology is eventually determined to be feasible, safe, and ethical.

1. Background

1.1 The cause

As part of our work to investigate potential focus areas within the category of scientific research, we became aware of a relatively new technology called “gene drives” (see this New York Times article for an overview).

One important potential application of gene drives that has been discussed is to prevent the spread of malaria by significantly reducing the population of mosquitos that can carry it.1

According to the World Health Organization (WHO), 438,000 people died from malaria in 2015.2 Our interest in this technology is driven by the potential, if it can be deployed safely and effectively, to substantially reduce this figure.

Many questions about the potential development and deployment of gene drives sit at the intersection of science and policy. Accordingly, our investigation of the topic has explored it from both perspectives, led by staff members who focus on each of science and policy (including scientific advisors).

1.2 The organization

The Foundation for the National Institutes of Health (FNIH) was established by Congress in 1990 as a not-for-profit 501(c)(3) charitable organization to support the mission of the National Institutes of Health (NIH). The FNIH procures funding, manages inter-institutional relationships, works with partner institutions, and provides other support to help accelerate biomedical research.3

2. About the grant

2.1 Proposed activities

FNIH proposes to convene a working group of approximately twenty experts to develop a consensus recommendation on a pathway for field testing gene drives focused on population modification or population suppression of mosquitoes in an effort to significantly reduce the burden of malaria in Sub-Saharan Africa. The working group will aim to include experts in malaria research as well as insect containment/quarantine, mathematical modeling, epidemiology, clinical trial design, and regulatory science. The working group will also aim for geographic diversity and representation from the World Health Organization and the New Partnership for Africa’s Development (an African Union technical advisory body).

The FNIH plans to hold three meetings of the working group in different countries, then to conclude the process by publishing a set of recommendations in an open-access peer reviewed journal. The anticipated timeline for this work is around 18 months.

One specific question we expect the working group to address is whether the field testing pathway should, in addition to cage and other field trials, include a self-limiting release.4 We are interested in learning from the working group’s process what sorts of questions or risks a self-limiting release might address and whether they are sufficiently important to warrant the associated delay.

2.2 Budget and room for more funding

The FNIH’s proposed budget for this project is $1,228,845. Absent our funding we think it is fairly likely that BMGF would have funded the creation of the working group, but we do not consider this a strong reason not to make this grant because we would guess that the counterfactual use of their malaria funds is likely to be quite cost-effective.

2.3 Case for the grant

Our understanding is that there is not yet consensus on what a pathway for field testing gene drives focused on modifying or suppressing vector mosquito populations should look like. Our guess is that developing such a consensus path might help accelerate the identification and redress of technological, ethical, and regulatory issues, leading to a faster eventual timeline for deployment if it is determined to be appropriate. We also believe that supporting this project is likely to help us better understand the open questions and any disagreements between key parties.

The FNIH seems to us to be well-positioned to lead the process of developing a consensus proposal. Our understanding is that the FNIH (working with funding from BMGF) has been instrumental in supporting gene drive research to date, and that it has experience convening groups of this nature. For instance, it co-organized with WHO a similar report on consensus standards for testing non-gene-drive genetically modified mosquitoes (GMMs) in the past.5 That report was opened for public comment in 2012, and was subsequently incorporated into a WHO guidance framework that was published and adopted in 2014.6 The FNIH also co-sponsored a recent report from the National Academies of Sciences on responsible conduct of gene drive research.7

As mentioned above, the main positive effect we hope this grant could have is reducing deaths from malaria, though we think the grant could also have a smaller positive impact by accelerating a regulatory rejection of gene drive technology (and thereby freeing up research funding and effort for other things) if that turned out to be appropriate. In terms of reducing deaths from malaria, we think a natural comparison point to use is a grant to the Against Malaria Foundation (AMF), the top recommended charity of our sister organization, GiveWell. Roughly speaking, we estimate that this $1.2 million grant would be more cost-effective than a similarly sized grant to AMF if it relieved two days worth of future malaria burden (more details on this estimate in the footnote).8

Though we see it as a bet worth taking, we think there is a very considerable likelihood that this grant never affects malaria burden at all, for any number of potential reasons, falling into two main buckets:

  • The working group doesn’t have any impact on gene drive development:
    • The working group fails to develop consensus.
    • The consensus recommendations are fairly obvious, and so don’t argue for any changes relative to current plans.
    • The consensus recommendations are never adopted by key regulatory bodies, and so projects have to follow the same path they would have had to otherwise.
  • Gene drives don’t affect malaria:
    • Gene drive technology turns out not to work or to be unsafe to deploy.
    • Authorization for gene drive deployment turns out to be impossible to achieve.
    • Another technology leads to malaria eradication prior to gene drive having any impact.

Though we think these risks jointly make it quite unlikely that this grant will have any impact on malaria, we see the possibility that it could have a significant impact by leading to faster field testing timelines as sufficient to justify the grant.

2.4 Risks and reservations about this grant

We find it plausible that this project could potentially cause an unnecessary delay in the deployment of gene drives to reduce the burden of malaria. If the working group consensus process produces a recommendation that commits researchers working on anti-malaria gene drives to a sub-optimal testing pathway, safe and ethical deployment could take place at a later date than would have been the case in the absence of the working group. We think this is unlikely and that the risk of our grant causing this outcome is mitigated by the likelihood that another funder would have supported it in our absence.

3. Plans for learning and follow-up

We do not expect to produce any updates on this grant until after the working group has completed its work, though we are hoping to attend its meetings if scheduling allows. Once the committee has completed its work, we plan on writing a public review of that work and an update about this grant.

Key questions we will follow up on include:

  • Did the working group reach a consensus on a plan that seems likely to reduce uncertainty about the field testing path for a malaria gene drive?
  • What, if any, disagreements arise during the working group’s convening?
  • What do we think about the consensus path recommended by the group?
  • Do other organizations (e.g., the WHO) ultimately support the consensus of the group?

4. Sources

DOCUMENT SOURCE
Esvelt et al. 2014 Source (archive)
FNIH, About Us Source (archive)
GiveWell, Against Malaria Foundation Source
MIT Technology Review, The Extinction Invention Source (archive)
National Academies of Sciences, Engineering, and Medicine, Gene Drives on the Horizon Source (archive)
New York Times, Gene Drives Offer New Hope Against Diseases and Crop Pests Source
Roll Back Malaria, About RBM Source (archive)
Sculpting Evolution, Gene Drive FAQ Source (archive)
Statista, Impact of mosquito-borne diseases worldwide in 2015 Source (archive)
Statista, Sustained Progress in the Worldwide Fight Against Malaria Source (archive)
WHO, 10 facts on malaria Source (archive)
WHO, Guidance Framework for testing of genetically modified mosquitoes Source (archive)
WHO, Progress and prospects for the use of genetically modified mosquitoes to inhibit disease transmission Source (archive)
WHO, World Malaria Report 2015 Source (archive)