RESEARCH ARTICLE - Am MIT spezialisierte KI-Forschung

RESEARCH ARTICLE

Funding CRISPR: Understanding the role of
government and philanthropic institutions
in supporting academic research within
the CRISPR innovation system

David Fajardo-Ortiz1,2
Maywa Montenegro de Wit4

, Stefan Hornbostel3

,
, and Annie Shattuck5

1Research System and Science Dynamics Research Area, Deutsche Zentrum für Hochschul-und
Wissenschaftsforschung (DZHW ), Berlin, Deutschland
2Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgien
3Institut für Sozialwissenschaften, Humboldt-Universität zu Berlin, Berlin, Deutschland
4Environmental Studies Department, University of California Santa Cruz, Santa Cruz, CA, USA
5Department of Geography, Indiana University, Bloomington, IN, USA

Schlüsselwörter: funding of science, genome editing technology, philanthropy, UNS. governmental
agencies

ABSTRAKT

CRISPR/Cas has the potential to revolutionize medicine, agriculture, and biology.
Understanding the trajectory of CRISPR research, how it is influenced, and who pays for it is an
essential research policy question. We use a combination of methods to map, via quantitative
content analysis of CRISPR papers, the research funding profile of major government agencies
and philanthropic organizations and the networks involved in supporting key stages of
high-influence research, nämlich, basic biological research and technological development.
The results of the content analysis show how the research supported by the main U.S.
government agencies focuses both on the study of CRISPR as a biological phenomenon and
on its technological development and use as a biomedical research tool. UNS. philanthropic
Organisationen, with the exception of HHMI, tend, by contrast, to specialize in funding CRISPR
as a genome editing technology. We present a model of cofunding networks at the two
most prominent institutions for CRISPR/Cas research (the University of California system and
the Broad/Harvard/MIT system) to illuminate how philanthropic organizations have articulated
with government agencies to cofinance the discovery and development of CRISPR/Cas.
Our results raise fundamental questions about the role of the state and the influence of
philanthropy over the trajectory of transformative technologies.

Keine offenen Zugänge

Tagebuch

Zitat: Fajardo-Ortiz, D., Hornbostel,
S., Montenegro de Wit, M., & Shattuck,
A. (2022). Funding CRISPR:
Understanding the role of government
and philanthropic institutions in
supporting academic research within
the CRISPR innovation system.
Quantitative Science Studies, 3(2),
443–456. https://doi.org/10.1162/qss_a
_00187

DOI:
https://doi.org/10.1162/qss_a_00187

Peer Review:
https://publons.com/publon/10.1162
/qss_a_00187

Erhalten: 31 Mai 2021
Akzeptiert: 1 Marsch 2022

Korrespondierender Autor:
David Fajardo-Ortiz
davguifaj@gmail.com

Handling-Editor:
Ludo Waltman

Urheberrechte ©: © 2022 David Fajardo-Ortiz,
Stefan Hornbostel, Maywa Montenegro
de Wit, and Annie Shattuck. Published
under a Creative Commons Attribution
4.0 International (CC BY 4.0) Lizenz.

Die MIT-Presse

EINFÜHRUNG

CRISPR/Cas is a set of versatile technologies aimed to manipulate, analyze, and visualize the
biomolecular machinery of living organisms (Pickar-Oliver & Gersbach, 2019). CRISPR/Cas
has the potential to revolutionize medicine (Diener & Tector, 2017; Kannan & Ventura,
2015; Schermer & Benzing, 2019), agriculture (Gao, 2018), and the way we understand life
selbst (Ledford, 2015). The impact of CRISPR/Cas genome editing technologies has been rec-
ognized with the 2020 Nobel Prize in Chemistry awarded to Emmanuelle Charpentier and
Jennifer A. Doudna “for the development of a method for genome editing” (Uyhazi & Bennett,

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Funding CRISPR

2021). Applications for these technologies have been proposed in fields as diverse as pharma-
ceuticals (Lu, Livi et al., 2017), crop development (Chen, Wang et al., 2019), livestock breed-
ing (Petersen, 2017), industrial biotechnology (Donohoue, Barrangou, & Mai, 2018), and pest
Kontrolle (McFarlane, Whitelaw, & Lillico, 2018). As CRISPR/Cas represents one of the most
potentially transformative technological breakthroughs of the last decade, it is important for
researchers, policymakers, and the public to understand innovation trajectories, who finances
ihnen, who bears the risks and rewards of innovation, and for whom technologies are ultimately
developed. CRISPR/Cas has been analyzed using myriad historical, legal, ethisch, Politik, Und
scientometric approaches. The social science and humanities discussion on CRISPR/Cas tech-
nologies ranges from ethical concerns about heritable genome editing (Reyes & Lanner, 2017) Zu
intellectual property (Parthasarathy, 2018; Sherkow, 2017) and democratization and gover-
nance of these technologies (Montenegro de Wit, 2020). Despite the diversity of such studies,
the role of financing on CRISPR/Cas research—specifically how different types of funding influ-
ence the research process—remains largely opaque.

Since the Second World War, in the period known as the golden age of capitalism, govern-
ment agencies have been the main source of funding for scientific research in the U.S. academy
(Geiger, 2008). Breakthrough technologies have emerged from long-term investments in R&D
under the banner of a “public good” mission (Mazzucato, 2015). Amid the growing influence
of productivist coalitions since the 1930s—farm commodity groups, land-grant administrators,
agribusiness firms, and federal agricultural agencies (Buttel, 2005)—government agencies
have largely taken the lead in actively shaping markets and shouldering the risk of
early-stage transformative research investments (Mazzucato, 2015). Private-sector actors typ-
ically limited their role to lower risk forms of technology integration, Entwicklung, und Mar-
keting later in the innovation process. This status, during a period of corporate consolidation,
is less contradictory than it first appears. A schism between “basic” and “applied” science has
long been recognized as favorable to private-sector interests who actively worked to carve a
social division of labor that put universities in charge of basic research and positioned industry
to control the commodity form (Kloppenburg, 2005). Though recognized as a taxpayer subsidy
to agribusiness in the agricultural sector (Glenna, Lacy et al., 2007), this relationship has not
only withstood time but has deepened: With the passage of Bayh-Dole in 1980, Congress fun-
damentally shifted the incentive structure governing research and development by allowing
publicly funded institutions to own inventions resulting from federally sponsored research
and to license those inventions to the private sector (Boettiger & Bennett, 2006).

Early research progress on genome technologies (viral vectors, RNAi, and the different genome
editing platforms) largely followed this pattern, with the U.S. Nationale Gesundheitsinstitute (NIH)
playing a leading role in funding innovation over the past 30 Jahre (Fajardo-Ortiz, Shattuck, &
Hornbostel, 2020). Scientometrics studies on the impact of U.S. government institutions, wie zum Beispiel
the National Science Foundation and the NIH, show that these institutions still function as global
driving forces of innovation writ large (Chen, Roco et al., 2013; Li, Azoulay, & Sampat, 2017).

Jedoch, there has been a clear decline in U.S. government support for science in recent
years when measured as a percentage of gross domestic product (Boroush, 2020), while
simultaneously a second golden age in the economic power of philanthropic and charitable
organizations is taking place in the United States (Stevens, 2019). The emerging active role of
philanthropic foundations as patrons of science has serious implications for the governance
of science and technology. Zum Beispiel, Anne-Emanuelle Birn has documented the capacity
of philanthropy to change the global research agenda on health from a focus on the social
determinants of health to sophisticated technological solutions, with mixed results (Birn,
2014). Ähnlich, the participation of philanthropic organizations in the area of agriculture

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and food sciences is currently promoting the development and implementation of “silver bul-
let” technologies that allow the incorporation of farmers into commercial value chains
(Brooks, 2013). Darüber hinaus, an investigation into the role of science philanthropy in U.S.
research universities showed how this type of organization concentrates universities’ efforts
on the translation of knowledge from basic research to the development of applications,
much like other private sector actors (Murray, 2013). Understanding how different types of
funding accrue to and support different levels of research—from basic science to the devel-
opment of technologies to their ultimate application in specific industries—can provide us
with fundamental information on the influence of these different organizational actors on
the development and implementation of CRISPR/Cas technologies.

The University of California system and the Broad/Harvard/MIT system1 are the two most
prominent academic institutions involved in the research and development of CRISPR/Cas tech-
nologies. The impact of these two research systems on the invention and development of
CRISPR/Cas technologies has been well documented (Cockbain & Sterckx, 2020; Fajardo-Ortiz
et al., 2020; Parthasarathy, 2018). daher, these institutions are an excellent case study to
examine the evolution of these technologies, the funding networks that support them, und das
relationships between innovation, financing, production, and property rights over these technol-
ogies. In the present investigation we aim to map and critically analyze the organization of the
cofunding networks of highly cited research on CRISPR/Cas technologies performed by the UC
and the Broad/Harvard/MIT systems. Wichtig, while the University of California is a public
institution, the Broad/Harvard/MIT system is made up of private institutions. Diese Unterscheidung ist
relevant for the study of university research funding, as differences have been reported in terms
of the ability to access government and philanthropic funding between public and private uni-
versities (McPherson, Gobstein, & Shulenburger, 2010; Taylor, 2016; Zhang, 2019). Doing so
raises fundamental questions about the articulation between government agencies and philan-
thropic organizations in supporting breakthrough innovations, risk, reward, and democratic
influence over the trajectory of transformative technologies.

Our analysis focuses on the initial stages of the CRISPR/Cas innovation process that take
place in academic institutions. In this sense, we focus on two types of research published
in scientific journals (Tisch 2; see Section 2). The first type of research relates to the study
of CRISPR as a biological phenomenon, das ist, as a component of the bacterial immune sys-
tem. This category is important because it is the source of the necessary scientific knowledge
that allows the continuous development of CRISPR/Cas technologies. Zum Beispiel, the original
invention of the CRISPR/Cas9 system as a genome editing technology (Jinek, Chylinski et al.,
2012) was strongly based on a number of previous scientific discoveries, such as the role of
small RNAs for sequence-specific detection and silencing of viral nucleic acids (Wiedenheft,
Sternberg, & Doudna, 2012) or the role of RNase III in bacterial immunity (Deltcheva, Chylinski
et al., 2011). Basic research on CRISPR/Cas as a biological phenomenon has not ended and
continues to provide scientific knowledge for the subsequent development of CRISPR/Cas tech-
nologies. The second type of research is related to the continuous development of CRISPR/Cas
technologies, das ist, the set of investigations subsequent to the original invention of
CRISPR/Cas9 genome editing system. The continuous development of CRISPR/Cas technolo-
gies is oriented to extending the use of CRISPR/Cas to different organisms and cell types,
increasing the specificity of CRISPR/Cas, and the search for platform alternatives to Cas9 that
could overcome the foundational intellectual property restrictions on prior inventions. Diese

1 The Broad/Harvard/MIT system comprises Harvard University, the Massachusetts Institute of Technology,
and the Broad Institute, an independent research nonprofit that partners with MIT and Harvard. Dafür
Studie, we included research conducted at all three institutions in this system.

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categories do not include research where CRISPR/Cas is used primarily to investigate or change
the function of genes in target organisms, including analyzing the role of specific genes in nor-
mal or pathological biological processes and applications of CRISPR/Cas in biomedicine, food
Systeme, environmental systems, or industrial biotechnology. For the purposes of this analysis,
we also excluded papers reporting the ethical or societal implications of CRISPR/Cas.

While basic research on CRISPR as a biological phenomenon provides the scientific knowl-
edge necessary for the invention of CRISPR/Cas technologies, research related to the develop-
ment of CRISPR/Cas technologies is central to downstream applications and IP rights, and thus
beneficiaries of this technological revolution. In this regard, we seek to illuminate how philan-
thropic and charitable organizations have engaged with U.S. government agencies to cofinance
the discovery and development of CRISPR/Cas technologies from a macroscopic perspective of
major U.S. philanthropic and governmental funding sources, and from a perspective focused on
research funding at the University of California and the Broad/Harvard/MIT systems. To get a
macroscopic perspective, we coded the content of CRISPR publications funded by the four
largest U.S. government agencies and four largest U.S. philanthropic organizations. For the
focused perspective, we mapped the cofunding networks for highly influential research that
took place at the University of California and the Broad/Harvard/MIT systems. This method
may be useful as a research policy tool to allow decision makers to visualize influence on
public sector agencies over the direction of technological development.

2. METHODOLOGY

To get a codified overview of the CRISPR research portfolios of major U.S. government
agencies and philanthropies, we combined VOSviewer’s scientometric analysis (Van Eck &
Waltman, 2017) and KH Coder’s text mining tools (Higuchi, 2016) as follows:

Im Februar 2022, we conducted a search for papers on CRISPR in the Web of Science
( WoS) (Mongeon & Paul-Hus, 2016) using the following criteria: CRISPR or “clustered
regularly interspaced short palindromic repeats” (Topic) and Articles (Document Types).
We found 22,834 Papiere.

2. With the bibliometric information from WoS, we built a co-occurrence network model of rel-
evant terms related to CRISPR research (Figur 1). The clustering analysis identified six clusters
in the co-occurrence network. The three largest clusters are related to biological and patho-
logical processes mainly at the cellular level (d.h., CRISPR as a research tool (red nodes));
CRISPR as a component of the innate immune system of certain bacteria and archaebacteria
(d.h., CRISPR as a biological phenomenon (blue nodes)); and CRISPR as a genome editing
Technologie (green nodes). We coded the terms with the highest total link strength from the
three main clusters into the following categories: phenomenon, Technologie, and research tool.
3. From WoS, the bibliometric information (title, abstract and keywords) of the research
articles that report funding from the following entities was downloaded: National Insti-
tutes of Health (NIH): 6,218 Papiere; Nationale Wissenschaftsstiftung (NSF): 1,092 Papiere;
United States Department of Defense (DoD): 341 Papiere; UNS. Department of Energy
(DoE): 255; Howard Hughes Medical Institute (HHMI): 329; Burroughs Wellcome Fund
(BWF): 155 Papiere; Bill & Melinda Gates Foundation (BMGF): 111 Papiere; und das
Welch Foundation (TWF): 104 Papiere.

4. The content (title, abstract and keywords) of the articles financed by these organizations
was analyzed with KH Coder using the coding built in the previous steps. A heat map
and clustering were generated by crossing the categories “phenomenon,” “technology,”
and “research tool” with the sources of financing analyzed.

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Figur 1. Co-occurrence map of relevant terms in articles on CRISPR.

Search criteria, number of papers found in the Web of Science ( WoS), number of papers selected and number of papers forming the
Tisch 1.
cofunding network models. It is important to note that because of the historical relevance of Cas9 and Cas12a as the first two CRISPR platforms
for genome editing (Ishino, Krupovic, & Forterre, 2018) we use them as additional terms in the search criteria, and the search for terms in WoS
was carried out as a full-text search, not limited to terms in the title. Daher, although we did not explicitly search for the different nucleases (Und
their pseudonyms), any paper with a term associated with CRISPR will appear in the search. This scope is important because the two university
systems have distinct IP rights over the Cas variants and we aimed to be as inclusive as possible.

Broad/Harvard/MIT System

Search criteria:

ORGANIZATION-ENHANCED: (Broad Institute or Massachusetts Institute of Technology (MIT) or Harvard University) AND TOPIC:
(CRISPR or “clustered regularly interspaced short palindromic repeats” or Cas9 or Cpf1 or Cas12a). Refined by: DOCUMENT TYPES:
(ARTIKEL)

Total of papers found in the WoS (by April 25, 2020)

Total of papers selected from WoS with at least 25 citations (receiving 95.2% of citations)

922

364

University of California System

Search criteria:

ORGANIZATION-ENHANCED: (University of California System) AND TOPIC: (CRISPR or “clustered regularly interspaced short

palindromic repeats” or Cas9 or Cpf1 or Cas12a). Refined by: DOCUMENT TYPES: (ARTIKEL)

Total of papers found in the WoS (by April 25, 2020)

Total of papers selected from WoS with at least 15 citations (receiving 94.8% of citations)

920

400

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Tisch 2.

Research levels of the papers in the network models

A. Biological phenomenon

Papers investigating CRISPR/Cas as bacterial immune systems; the interactions of their
component in bacteria or archaea, and/or the molecular, ecological, or evolutionary
interactions of these systems with the bacteriophage viruses.

B. Developments or improvements of

These papers report discoveries of alternative CRISPR/Cas genome editing systems that

CRISPR/Cas technologies

C. Other

could be more efficient, more versatile, or easier to use; investigations aimed to
overcome the technical difficulties to apply the technology in different organisms; oder
investigations reporting molecular mechanisms that can be used to modulate the
activity of Cas enzymes.

Papers in which CRISPR/Cas is not the central object of investigation but is an instrument
to identify or analyze the role of specific genes in normal or pathological biological
processes; papers reporting applications of CRISPR/Cas in biomedicine, food systems,
environmental systems, or industrial biotechnology; or papers reporting the ethical or
societal implications of CRISPR/Cas technologies.

To build the funding network for highly cited research on CRISPR produced by the Univer-

sities of California and the Broad/MIT/Harvard systems, we follow these steps:

5. A search of peer-reviewed papers was performed in WoS in May 2020. The research
criteria are listed in Table 1. A very similar number of papers was found for the UC sys-
tem and the Broad/Harvard/MIT system (920 Und 922 jeweils; siehe Tabelle 1). Für
each system we selected a number of top-cited papers that concentrated approximately
95% of the citations received. Das ist, we wanted to focus our explorative analysis on the
most influential papers from each institutional system. Roughly 40% of top-cited papers
accumulated 95% of citations, while the remaining 60% of papers received just 5% von
citations (Tisch 1).

6. A bimodal network model of papers and cofunding organizations was built for each
institutional system by using the information reported in the acknowledgment section
of the papers.

7. The papers in the bimodal network models were classified into three different types of

Forschung (Tisch 2).

8. The cofunding organizations in the bimodal network models were classified as follows.
A: UNS. government agencies—any public source of funding in the United States
including federal, state, and local agencies, and armed forces. B: Philanthropic or char-
itable organizations (d.h., nonprofit organizations that are tax exempt under 501(C)(3)
requirements in the United States (Bertrand, Bombardini et al., 2020)). C: Other organi-
zations, such as academic institutions, professional organizations, medical research
Zentren, and non-U.S.-based organizations.2

9. A bimodal network model of papers and cofunding organizations was built for each insti-
tutional system by using the information reported in the acknowledgment section of the
Papiere. The cofunding network models were visualized and analyzed with Cytoscape

2 Here it is necessary to clarify that Howard Hughes Medical Center, an influential node in our network
Modell, is a center for basic and applied academic medical research and is often thought of primarily as
a research institution. Jedoch, its most recent 990 (publicly available tax form for the period ending
August 2019) zeigt an $1.3 billion in investment income from its endowment, dwarfing the grants it received ($2.8 Million) and its program service revenue ($2.6 Million). It gave out $34 million in grants
(ProPublica, 2019). Given its 501(C)(3) status and its financial statements, we included HHMI in the
philanthropic and charitable organization category.

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(Saito, Smoot et al., 2012). Only those papers that were classified as (A) research on
CRISPR as a biological phenomenon and (B) research aimed at the development and
improvement of CRISPR/Cas technologies were included in the bimodal network
Modelle. Likewise, only those institutions based in the United States classified as (A) gov-
ernment agencies and (B) philanthropic or charitable organizations were included in the
network model. Endlich, only those organizations that funded at least three CRISPR inves-
tigations (type A or B) from the previously selected sets of highly cited articles were
enthalten.

3. ERGEBNISSE

KH Coder generated a heat map and clustering from the tabulation of the terms coded in the
categories “phenomenon,” “technology,” and “research tool” versus the different sources of
financing analyzed (Figur 2). The heat map and clustering clearly identify three different pro-
files of entities that fund CRISPR research. A first profile is characterized by a relatively high
percentage of articles with terms related to the categories “phenomenon” and “technology”
(Figur 2). Such is the case for the DoE and the NSF, which appear aggregated in the same
cluster. A second profile is characterized by a high percentage of articles with terms coded in
the technology category and relatively lower percentages of the other two categories (Figur 2).
The philanthropic organizations TWF, BMGF, and BWF follow this pattern. Endlich, a third
funding entity profile shows a balance between the terms related to the research tool and tech-
nology categories (Figur 2). Such is the case with the HIH, the DoD, and the HHMI.

A cofunding network model was built for each institutional system showing how philan-
thropic and charitable organizations articulated with U.S. government agencies to finance
the discovery and development of CRISPR/Cas technologies that took place at the University
of California and Broad/Harvard/MIT systems. The bimodal network model of the
Broad/Harvard/MIT system was formed by 28 Organisationen (12 governmental agencies and
16 philanthropic/charitable organizations) Und 111 highly cited papers (14 papers on CRISPR
as a biological phenomenon and 97 papers on the development of CRISPR/Cas technologies;
Figur 3). Almost half of this set of UC papers were authored by Jennifer Doudna (31 papers on
CRISPR as a biological phenomenon and 26 papers reporting developments of CRISPR/Cas
technologies). Andererseits, the bimodal network model of the UC system was formed
von 15 funding organizations (10 governmental agencies and five philanthropic/charitable

Figur 2. Heat map and clustering of coded categories versus philanthropic and government funders.

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Figur 3. The cofunding network model of top cited CRISPR/Cas research in the Broad/Harvard/MIT system. This is a bimodal network
model made of papers and funding sources. The size of the nodes representing papers is a function of the number of citations received.
The edges point to which organizations funded which papers. Only the nodes representing the top most-cited papers in the network model
(über 500 citations) are labeled with their title and year of publication and the red-lighted edges are linking them with their funding organi-
zation. Blue nodes represent governmental agencies while red nodes represent philanthropic/charitable organizations. It is important to specify
that the aggregation of funding sources is limited by the information that the authors provide in the acknowledgment section of the papers. Für
Beispiel, there are authors who generally report funding from the National Institutes of Health, and other authors inform from which institute in
particular they receive support.

Organisationen) Und 117 highly cited papers (59 papers on CRISPR as a biological phenomenon
Und 58 papers on the development of CRISPR/Cas technologies; Figur 3). Feng Zhang is the
author of a quarter (28 von 111) of the papers on the bimodal cofinancing network model of the
Broad/Harvard/MIT system while David R. Liu and George Church each authored 14 Papiere.

In the case of the Broad/Harvard/MIT system, the investigation on the development of
CRISPR/Cas technologies is grouped in three main clusters in the cofunding network model
(Figur 3). The three clusters are supported by the NIH, which occupies a central position
in the network model, but are cofunded by different sets or organizations. The cluster located
in the lower right corner of the network model is formed by papers cofunded by the NIH and
the Department of Energy (DoE); a second cluster (upper right corner) is cofunded by a set of
philanthropic and governmental organizations; and the third cluster (upper left corner) Ist
cofunded by the Howard Hughes Medical Institute (HHMI) together with a set of U.S. Militär
organizations or programs (Figur 3). There is also an important set of papers exclusively
funded by the NIH.

In the case of the University of California (UC), the cofunding network model (Figur 4)
suggests that the top-cited investigations on CRISPR as a biological phenomenon, welches ist
related to the discovery stage of investigation in which the basis of future technologies are
built, were mostly supported by the U.S. Department of Energy and the National Science
Foundation. A relatively smaller and less cited set of papers was cosupported by the Burroughs
Wellcome Fund together with the National Institutes of Health (NIH; Figur 4). Auf dem anderen
Hand, the investigations related to the development of CRISPR/Cas technologies at the UC
were mostly supported by the NIH together with the National Science Foundation and the
HHMI in two respective clusters of papers (Figur 4). There is also an important set of tech-
nological development papers funded by the NIH without the participation of other frequent
governmental or philanthropic/charitable funding sources (Figur 4).

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Figur 4. The cofunding network of top-cited CRISPR/Cas research in the UC system. This is a bimodal network model made of papers and
funding sources. The size of the nodes representing papers is a function of the number of citations received. The edges point to which orga-
nizations funded which papers. Only the nodes representing the top most-cited papers in the network model (über 200 citations) are labeled
with their title and year of publication and the red-lighted edges link them with their funding organizations. Blue nodes represent governmental
agencies while red nodes represent philanthropic/charitable organizations. It is important to specify that the aggregation of funding sources is
limited by the information that the authors provide in the acknowledgment section of the papers. Zum Beispiel, there are authors who generally
report funding from the National Institutes of Health, and other authors inform from which institute in particular they receive support.

It is important to mention that while the papers authored by Jennifer Doudna are distributed
throughout the bimodal network model, the papers of the three main authors associated with
Broad/MIT/Harvard are concentrated in different regions of the bimodal network model. Feng
Zhang’s articles are funded primarily by the charitable/philanthropic cluster of organizations
along with the NIH, while George Church’s papers, on the network model, are cofunded
primarily by NIH and DOE and David R. Liu’s research is located in the cluster of papers
cofinanced by HHMI in conjunction with the Department of Defense (DoD), the Defense
Advanced Research Projects Agency (DARPA) and the Defense Threat Reduction Agency
(DETRA).

4. DISKUSSION

The use of funding acknowledgment sections as a source of data for scientometrics studies has
been extensively discussed in recent years (Kokol & Vošner, 2018; Paul-Hus, Desrochers, &
Costas, 2016; Tang, Hu, & Liu, 2017). Jedoch, despite the enormous potential of using this
source of data to investigate the impact of funding entities on the development of science and
Technologie, some key considerations must be taken into account. Erste, our investigation was
based on information provided by WoS, which began systematically collecting acknowledg-
ments information in 2008 (Kokol & Vošner, 2018), becoming the de facto standard source for
this type of investigation. In that sense, a comparative analysis of the three main bibliometric
databases ( WoS, PubMed, and Scopus) found that WoS outperforms the other databases in

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terms of the proportion of articles with funding information (Paul-Hus et al., 2016). Zweitens,
social sciences, humanities, and non-English language journals are underrepresented in both
WoS and Scopus (Mongeon & Paul-Hus, 2016). In the case of WoS, speziell, the Arts &
Humanities Citation Index (AHCI) content is not indexed for funding acknowledgment data
and there are problems covering this information for non-English-language papers (Paul-Hus
et al., 2016), although information on the financing of the papers indexed in AHCI has recently
been added to WoS (Liu, Tang, & Hu, 2020). Dritte, a loss of funding information of 12% hat
been reported for WoS (Álvarez-Bornstein, Morillo, & Bordons, 2017). Das ist, 12% of the
funding sources in the acknowledgment sections of papers are not captured in the WoS data-
base. In the present investigation, even though WoS has systematized financing data, the name
of each reported organization was carefully reviewed and errors were corrected. Previous
studies reporting the use of funding acknowledgment sections focused on analyzing the
impact of specific funding sources by using traditional metrics such as the number of citations
per paper.

One way to understand the profiles of philanthropic and government funding sources for
CRISPR research is to classify funding sources as targeted, top down, and nontargeted, bottom
hoch. Das ist, es gibt, on the one hand, institutions that finance research following strategic
criteria to reorient research efforts to satisfy specific knowledge and technology needs. Ein
example of a targeted source of research funding would be the European Commission’s
FP7-health, which issues calls under priority research topics (Viergever & Hendriks, 2016).
At the other extreme, there are organizations that offer their research funding through open
competition based on academic merit. Such would be the case with HHMI (Tjian, 2015).
Between these two extremes, there are organizations with mixed approaches to research fund-
ing, such as the UK Medical Research Council (Viergever & Hendriks, 2016). Our content
analysis suggests that three of the top four sources of philanthropic funding for CRISPR
research in the United States, the BWF, TWF, and BMGF, tend to specialize in the develop-
ment of CRISPR as a technology. In the case of the BMGF and the BWF, their relative special-
ization in the development of CRISPR as a technology is to be expected, as both organizations
have a science financing strategy aimed at solving the great challenges of society (Burroughs
Wellcome Fund, 2021; Bill & Melinda Gates Foundation, 2022). TWF, for its part, focuses on
the development of chemistry in the State of Texas (Welch Foundation, 2022). Jedoch,
recently this foundation has shown interest in the subject of genome editing technologies
(Doudna, 2019). In the case of the NSF, this federal agency of the United States has a legal
mandate to support all fields of fundamental science and engineering (National Science Foun-
dation, 2018). This would explain the high percentage of articles funded by the NSF that
include terms related to both the study of CRISPR as a biological phenomenon and the devel-
opment of CRISPR as a genomic technology. In the case of the Department of Energy, the high
percentage of articles related to the study of CRISPR as a biological phenomenon can be
explained in part by the research work that Jennifer Doudna carried out at the Lawrence
Berkeley National Laboratory (Dabbar, 2021).

Our results show that the HIH, DoD, and HHMI maintain high percentages of articles
related to the development of CRISPR technologies and their use as a biomedical research tool
(Figur 2). The DoD is classified as a largely targeted research funding source (Viergever &
Hendriks, 2016). The DoD’s funding profile for CRISPR research can be explained in part
by two strategic goals in relation to this technology. The first objective is related to making
CRISPR a more secure technology by anticipating possible bioterrorist threats (Sanders,
2019). The second objective of the DoD in relation to the use of CRISPR is to protect the health
of its personnel exposed to carcinogenic agents, and for this it requires investing in basic

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biomedical research (Glasgow, 2021). For its part, NIH’s CRISPR research funding profile
aligns well with its mission “to seek fundamental knowledge about the nature and behavior
of living systems and the application of that knowledge to enhance health, lengthen life, Und
reduce illness and disability” (Nationale Gesundheitsinstitute, 2017).

As far as we know, this is the first time that funding acknowledgments have been used to
build and analyze the relationships between the structures of cofunding networks, the research
Ebene, and the type of funding sources. This methodology could allow policymakers,
researchers, and granting agencies to identify whether different types of research funding
(z.B., öffentlich, private, philanthropic, university-based) and different government agencies
(z.B., NSF, NIH) tend to fund certain areas of scientific knowledge, how they influence one
another, and what their impact is on highly influential science and technology development.

In the case of CRISPR/Cas, our results suggest that even though U.S. government agencies
extensively supported all levels of CRISPR/Cas research in both institutional systems, philan-
thropic organizations have concentrated participation in cofunding the development of
CRISPR/Cas technologies as opposed to basic biological phenomenon research. This is partic-
ularly true for the Broad/Harvard/MIT system, where research has clustered around particular
research themes. Hier, we observed relatively smaller philanthropic organizations clustering
around similar developments, while larger organizations were more likely to fund projects
independently of other charitable actors. This philanthropic funding comes on top of public
research dollars, potentially assisting, though also altering, the trajectory of publicly funded
Wissenschaft.

Using funding acknowledgments sections does not allow us to differentiate the impact of
the different sources of funding on each research project. Further investigations are needed to
analyze such differentiation. What our results do clearly show is that philanthropic organiza-
tions show a different behavior from government agencies when it comes to funding CRISPR
Forschung. Both the content analysis of the articles financed by the main sources of U.S.
research funding and the analysis of funding networks at UC and the Broad/Harvard/MIT
system show that unlike government agencies whose funding is more widespread, philanthropic
organizations focus on research related to specific developments of CRISPR/Cas technologies.
Particularly noteworthy is the concentration of numerous philanthropic organizations in funding
research spearheaded by Feng Zhang to improve CRISPR/Cas technologies through the search
for and development of new nucleases: enzymes which perform the critical “cutting” function of
the CRISPR/Cas system (Figur 3).

Our results raise questions about the role of philanthropy in influencing predominantly
publicly funded research trajectories and its potential contribution to the privatization of
reward from that public investment. Das ist, while society as a whole finances the innovation
process through government agencies—assuming most of the risks of investing in new areas of
knowledge and technology—for-profit actors tend to participate in later stages (Laplane &
Mazzucato, 2020; Mazzucato, 2015). Our results align with a model in which philanthropic
organizations may play an important role in furthering the socialization of risk and the privat-
ization of profits that comes from the basic/applied division of labor between the public and
private sectors (McGoey, 2014). Critical studies on the governance of the innovation process
in biotechnology, particularly the governance of CRISPR/Cas technologies, have largely over-
looked the important role of U.S. charitable and philanthropic organizations as powerful actors
that can redirect the trajectory of the development and application of genomic technologies in
favor of specific interests or sectors of society. In that sense, it is fundamental to further the
study of the interaction between transformative innovation and philanthropy. A first strategy

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would be to measure the impact of philanthropic grants by analyzing the expenditures of the
sponsored projects. A consortium of 33 UNS. public research universities is moving in that
direction by connecting the information on their sponsors, grants, project expenditures, Und
final products such as papers and patents (Owen-Smith, Lane et al., 2017). Bedauerlicherweise,
neither the University of California system nor the Broad/Harvard/MIT system participate in
this initiative. Another strategy would be to gather the views of researchers, administrators,
and philanthropic foundations on the impact of such grants in the development of
CRISPR/Cas technologies. Any strategy to deepen knowledge about the role of philanthropic
foundations in the development of genomic editing technologies necessarily requires a com-
mitment to transparency on the part of the various participating actors.

ACKNOWLEDGMENTS

This research was supported by the Alexander von Humboldt Foundation. We thank our col-
leagues from Deutsche Zentrum für Hochschul-und Wissenschaftsforschung (Berlin, Deutschland)
and El Colegio de la Frontera Sur (Chiapas, Mexiko,) who provided insight and expertise that
greatly assisted the research. This paper is our analysis and does not necessarily represent our
colleagues’ Ansichten.

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BEITRÄGE DES AUTORS

David Fajardo-Ortiz: Konzeptualisierung, Datenkuration, Formale Analyse, Akquise von Fördermitteln,
Untersuchung, Methodik, Projektverwaltung, Ressourcen, Visualisierung, Writing—original
Entwurf, Writing—review & Bearbeitung. Stefan Hornbostel: Konzeptualisierung, Akquise von Fördermitteln,
Aufsicht. Maywa Montenegro de Wit: Konzeptualisierung, Methodik, Writing—original
Entwurf. Annie Shattuck: Konzeptualisierung, Methodik, Writing—original draft.

COMPETING INTERESTS

The authors have no competing interests.

FUNDING INFORMATION

This research was funded through an Alexander von Humboldt Stiftung (https://www
.humboldt-foundation.de) postdoctoral grant to David Fajardo-Ortiz (grant number:
1195113). The funders had no role in study design, data collection and analysis, Entscheidung
to publish, or preparation of the manuscript.

DATA AVAILABILITY

The original source of information was WoS. The WoS data have been made available to
DZHW and KU Leuven under a paid license. We are not allowed to redistribute WoS data
used in this paper.

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Owen-Smith, J., Lane, J., Weinberg, B., Jarmin, R., Allen, B. M., &
Evans, J. (2017). The Institute for Research on Innovation &
Wissenschaft (IRIS) UMETRICS Initiative.

Parthasarathy, S. (2018). Use the patent system to regulate gene
Bearbeitung. Natur, 562(7728), 486–488. https://doi.org/10.1038
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Petersen, B. (2017). Basics of genome editing technology and its
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ProPublica. (2019). Howard Hughes Medical Institute Form 990 für
period ending August 2019. ProPublica Non-Profit Explorer.
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Taylor, B. J. (2016). The field dynamics of stratification among U.S.
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lenges and opportunities at HHMI. JAMA, 313(2), 133–135.
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Nobel Prize in Chemistry. Journal of Clinical Investigation, 131(1),
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