# Evolutionary Genetic Engineering in the Indo-Pacific: Conservation,
Humanitarian, and Social Issues

Floyd A. Reed
Department of Biology
University of Hawai‘i at Mānoa
<EMAIL_ADDRESS>
The Indo-Pacific region contains a unique mix of opportunities for the
development and use of genetic-pest-management, gene-drive, and gene-drive-
like technologies. Here I collectively refer to these technologies as
Evolutionary Genetic Engineering (EGE). Indo-Pacific Islands have some of the
world’s highest rates of endemism and extinction—species and entire ecosystems
are at risk. This threat to the natural world is coupled with the burden of
human diseases, many of which are new and emerging or neglected tropical
diseases. The same factors which have led to high rates of endemism also, in
some ways, make this region an ideal testing ground for some types of EGE’s.
There is great potential for positive humanitarian, economic, and conservation
applications of EGE’s. However, these types of new technologies will be
initially viewed from the perspective of the recent history of a loss of self
determination, issues of social justice, and the testing of new technologies
(e.g., biocontrol, agricultural, nuclear) in the Indo-Pacific—a region of the
world that is still extensively colonized and controlled by Western Nations.
Experience with successes and failures in related technologies suggests a path
to move forward—a set of eight recommendations—to maximize the potential
payoffs and minimize unintended negative effects of EGE’s.

## Introduction

The Island Indo-Pacific is a large, important, unique, and unfortunately often
overlooked region of the world. There is tremendous potential for the positive
use of Evolutionary Genetic Engineering (EGE) in the region in both
humanitarian and conservation applications. This potential stems from the
regions geographic isolation, collection of infectious diseases, and species
conservation urgencies. However, it would be a mistake to neglect the context
of recent and ongoing political and social challenges in the region. Doing so
is likely to generate a negative reaction that could inhibit the applications
of promising emerging technologies. This context includes issues of
colonialism, self determination, biocontrol, the testing of new technologies,
and early experiences with genetically modified agricultural crops in the
region. In this article I am focused on the Island Indo-Pacific Tropics, but
also use examples from the broader region including India and Australia. I am
also focusing on terrestrial applications of EGE’s. There are potential
freshwater and marine applications, but this is less developed and goes beyond
the scope of the current article.

In order to move forward in a way that does not sacrifice long term progress
for short term convenience, we must accept that everyone has a role to play in
shaping our technological future; this is not always easy to do when faced
with confrontations and fundamental disagreements. To do this we must

  1. 1.

enhance communications and avoid a reluctance to provide more detailed
information about new technologies or to be dismissive of inquiries.

  2. 2.

EGE applications should only be pursued if there is a genuine benefit to the
local population (and if the people potentially affected generally agree that
this is desirable rather than the decision being made externally), not in
order to test new technologies in a “safe” manner or to avoid jurisdictional
regulations.

  3. 3.

The potential benefits and risks of EGE’s, along with the degree of
uncertainty surrounding both, need to be unambiguously communicated.

  4. 4.

There needs to be a frank discussion of unintended side effects and the
potential for misuse of the technology.

  5. 5.

Humanitarian goals need to be administered and controlled by humanitarian
organizations while conservation goals need to be administered and under the
control of conservation organizations (applicable to both governmental and
non-governmental organizations); this is especially true in an international
setting.

  6. 6.

Proactive research needs to be conducted and the data available to address
common concerns about the possible ecological and health effects of EGE’s.

  7. 7.

It takes broad perspectives, beyond what any single person is capable of, to
identify potential promises and pitfalls of the development and
implementations of EGE’s.

  8. 8.

Finally, a broad-based community discussion of, and direct involvement in, EGE
development and applications should occur as early as possible. This will
positively shape both the development and applications of the technology and
help build a solid social foundation for future developments.

## Potential Evolutionary Genetic Engineering Applications in the Island Indo-
Pacific.

The Indo-Pacific spans half of the Earth’s circumference yet receives
relatively less international focus. A revealing example is that this is the
non-polar region that is most often divided on map projections of the world.
This inattention is not simply due to a smaller population; the four most
populous countries in the world (China, India, the USA, and Indonesia) have
territory and active interests in the region.

The Island Indo-Pacific has some of the world’s highest rates of both species
endemism (unique genetic diversity) and extinction (Vitousek, 1988; Fleischer
et al., 1998; Myers et al., 2000; Kier et al., 2009). Adaptive radiations of
species here have served as prime examples of evolutionary biology (p. 380
Darwin, 1845; Dobzhansky, 1973). Extinctions in these species-rich regions are
proceeding at an alarming rate (Pimm et al., 1995; Ganzhorn et al., 2001;
Fonseca, 2009; Loehle and Eschenbach, 2012; Régnier et al., 2015) and this is
predicted to be exacerbated by climate change (Benning et al., 2002; Mora et
al., 2013). The region is in dire need of effective conservation strategies
and potential Evolutionary Genetic Engineering (EGE) applications targeting
introduced species and diseases have been proposed to establish effector genes
refractory to introduced vectored disease (genetic modifications to block
transmission of the disease) and genetic sterile insect techniques to suppress
populations of invasive species (Clarke, 2002; Wimmer, 2005; Sinkins and
Gould, 2006; Altrock et al., 2010; Esvelt et al., 2014; Reeves et al., 2014;
Webber et al., 2015).

The Island Indo-Pacific is also home to newly emerging and/or neglected
tropical diseases that affect human health as well as economically important
species. Vector borne human diseases in the region include chikungunya, dengue
fever, Japanese encephalitis, lymphatic filariasis, malaria, plague and Rift
Valley fever (in Madagascar), schistosomiasis, scrub typhus, West Nile fever,
and zika. Additionally there are diverse agricultural crop pests and diseases
that impact food production across the region. A major goal of EGE development
is to address human disease, and there is also potential for agricultural
applications (Alphey, 2002; Sinkins and Gould, 2006; Gould, 2008; Wimmer,
2013; Esvelt et al., 2014; Champer et al., 2016).

When countries are listed by gross domestic product per capita it becomes
apparent that the Indo-Pacific contains, in terms of national economic wealth,
many of the poorest countries in the world. For example, the Comoros,
Kiribati, Madagascar, Marshall Islands, Micronesia, Papua New Guinea, Solomon
Islands, Tuvalu, and Vanuatu have an average per capita GDP of Intl.$2,387,
approximately 1/8th of the world average, Intl.$18,872 (International Monetary
Fund, 2016). This limits the resources available that these governments can
apply to humanitarian and conservation interventions and suggests an enhanced
value of international collaboration.

In many ways the terrestrial isolation that has led to the Indo-Pacific’s
tremendous biological diversity also makes the region ideal for some EGE
applications. Suppressing or modifying non-native invasive species is an
obvious place to start. However, what may be a pest in one location may be a
highly valued or important ecological species in another (e.g., nopal Opuntia
cacti are a highly valued component of Mexican cuisine and source of animal
fodder while considered an invasive species pest in Australia—Cactoblastis
cactorum has been used successfully as bio-control in Australia but is now
threatening native Opuntia in the Americas (Zimmerman et al., 2004). Proper
application of Type 1 and 2a EGE’s (Appendix A: Types of Evolutionary Genetic
Engineering) can leave a species genetically unmodified within its native
range, even with low levels of migration between islands or islands and
continents (Altrock et al., 2010, 2011; Láruson and Reed, 2016). The limited
and discrete partitioning of land area of islands make 100% local genetic
transformation or eradication of a species possible without resorting to type
2b or 3 EGE’s (Appendix A) and allows the application to proceed in a stepwise
fashion across multiple islands using limited resources.

## Colonialism, self determination, and the testing of new technologies

We have different perspectives depending on our experiences and social /
cultural identities, and we are all-too-often not aware of how our individual
perspective differs from others. In the middle of the abstract I used the
following sentence, “The same factors which have led to high rates of endemism
also, in some ways, make this region an ideal testing ground for some types of
EGE’s.” I chose the wording of this sentence carefully. What was your
reaction? For many of the people reading this article the sentence seemed
perfectly natural and flows into the ideas of the preceding and following
sentences. However, for some readers the phrase “testing ground” is likely to
stand out. Our reaction to this sentence is related to our perspective. For
many who do not live in the island Indo-Pacific it is easy to see the region
as something external to our daily lives and more disposable for testing and
experimenting. In contrast, for some the Indo-Pacific represents home, family,
work, and is also fundamentally connected to a cultural identity. I ask
readers to construct your own sentence connecting a place that is highly
valued to you personally (your hometown, where you live now, or a place of
historical, religious, or cultural importance) with a “testing ground” of a
new potentially powerful technology with its own set of concerns and unknowns.

The Indo-Pacific has a long and continuing history of a loss of self
determination and sovereignty. The UN Special Committee on Decolonization
lists American Samoa, French Polynesia, Guam, New Caledonia, Pitcairn, and
Tokelau as Non-Self-Governing-Territories. The total number of ongoing
sovereignty disputes encompasses many more islands and regions too extensive
to list here. Colonization includes the establishment of extensive military
bases and use of the islands for tests of nuclear, biological, and chemical
warfare technologies—and these were not limited to a few isolated incidents,
for example hundreds of nuclear weapons tests were conducted by France in
Mururoa and Fangataufa Atolls, by the United Kingdom in South Australia,
Montebello, and Kiritimati Islands, by the United States in Pikinni (Bikini),
Ānewetak (Enewetak), Johnston (Kalama) Atolls, and Kiritimati. This history of
military testing, non-military testing of new technologies (e.g., disastrous
attempts at classical biological control by introducing new species, e.g.,
Howarth 1983; Clarke et al. 1984; Henneman and Memmott 2001; Messing and
Wright 2006; Hays and Conant 2007; Parry 2009), and colonization in the region
can severely inhibit international biological research and potential
applications including EGE’s.

There is a case study that deserves special mention within the context of
EGE’s in the Indo-Pacific, especially in the context of international programs
and applications of mosquito genetic engineering. From 1969–1975 the World
Health Organization (WHO) collaborated with the US Public Health Service (PHS)
and the Indian Council of Medical Research (ICMR) to establish a Genetic
Control of Mosquitoes Research Unit (GCMRU) in India; this was financially
supported by the Government of India, US PL-480 funds, and the CDC (American
Embassy New Delhi, 1975a). The GCMRU was studying and implementing mosquito
control technologies including the release of sterilized individuals. What
appears to have started with concerns about a carcinogen (thiotepa) being
added to well water in the village of Pochanpur without public or government
consultation got caught up in politics (American Embassy New Delhi, 1975b;
Hanlon, 1975), with widespread accusations in the media and later by the
Government of India, and grew into a political disaster with suspicions that
the US military was using India to test methods of biological warfare using
mosquitoes (American Embassy New Delhi, 1974; Sehgal, 1974; Anonymous, 1975;
American Embassy New Delhi, 1975b; Hanlon, 1975; Anonymous, 1976; Powell and
Jayaraman, 2002). The addition of thiotepa to village water has been denied by
WHO (Tomiche, 1975), but publications preceding the accusations suggest this
may have happened (pp. 85-87 Pal, 1974)—and therein lies one problem. There
was a lack of clear unambiguous communication from the beginning. Furthermore,
PHS did have military connections and shared materials and information with
the US military (Langer, 1967; Treaster, 1975). The US military did conduct
chemical and biological tests in the Indo-Pacific; this included the release
of mosquitoes off the coast of Baker Island (“Magic Sword” 1965), the release
of Bacillus globigii in O‘ahu (“Big Tom” 1965), shelling sarin nerve agent in
Waiākea Forest Reserve, Hawai‘i (“Red Oak” 1967), and the dispersal of
Staphylococcus aureus enterotoxin type B over Ānewetak (Enewetak) Atoll (“DTS
Test 68-50” 1968). However, in all likelihood there was no military or
biological warfare connections with the GCMRU (World Health Organization,
1976; Powell and Jayaraman, 2002). Covert transfer of US funds to keep GCMRU
going was briefly discussed with WHO (American Embassy New Delhi, 1975c;
Secretary of State Washington DC, 1975) but this was considered too risky and
the US suspended funding the project. Despite denials by WHO (Tomiche, 1975),
the GCMRU, which was planned to extend at least until 1978, was forced to shut
down prematurely in 1975 (American Embassy New Delhi, 1975d) and the project
was deemed a failure (Curtis, 2007).

What can be learned from this?

  1. 1.

There was a clear lack of communication resulting from a reluctance of either
the WHO or the US to engage the media and comment on the allegations (American
Embassy New Delhi, 1974, 1975e; Anonymous, 1975; Tomiche, 1975). This was
unfortunate as it, perhaps rationally, fuelled suspicions. The public
perception of public perception may differ from public perception—the
individual perception of public opinion is influenced by a range of factors
and may not be an accurate reflection of commonly held attitudes (e.g., Mutz,
1989). The idea that providing more information would undermine support
conflicts with recent results that show the more informed people are of the
release of genetically modified mosquitoes the more supportive they become;
however, a great deal of public engagement has to be accomplished, especially
for women, minorities, and people with lower education levels and lower
household incomes (Ernst et al., 2015; Kolopack et al., 2015).

  2. 2.

There was a perception that these experiments would not have been permitted in
Western countries and that India was being used as a testing ground
(Anonymous, 1975; Raghavan and Jayaraman, 1975). Knowledge that a technology
has been effective in other countries is one factor associated with strong
public support (Ernst et al., 2015). It is unfortunate that prior programs in
the US, Myanmar/Burma, Tanzania, Western Africa, and France were not
communicated to the Indian press (Laven et al., 1972; World Health
Organization, 1976; Curtis, 2007). The perception that an international
project is being conducted to avoid home country regulation should certainly
be (truthfully) avoided.

  3. 3.

The potential benefits of the project to the people of India was unclear
(American Embassy New Delhi, 1974; Anonymous, 1975). This is perhaps most
tragic of all. India suffers from mosquito vectored dengue, malaria, Japanese
encephalitis, chikungunya, and lymphatic filariasis (Sharma, 2015). While a
balance must be struck to not over-promise results that may not be realized,
the goals and potential benefits of EGE applications must also be clearly
advertised.

  4. 4.

There was a lack of an a priori open and frank discussion about possible
misuse of the technology (Hanlon, 1975). While any technology can be
potentially misused by individuals or organizations, a nation’s government,
and especially its military, has non-humanitarian and non-conservation
priorities that can potentially conflict with the goals of humanitarian and
conservation projects. Regardless of the existence of an actual conflict, the
perception of possible conflict does exist, which can undermine credibility
(Serafino et al., 2008; Charny, 2016). Fortunately today this is widely
recognized and the 1978 UN ENMOD treaty (http://www.un-
documents.net/enmod.htm) may prevent, depending on interpretation, military
involvement in EGE technologies except perhaps for some limited applications
of type 0 and 1 systems (Appendix A). The ENMOD treaty states that “Each State
Party to this Convention undertakes not to engage in military …environmental
modification techniques having widespread, long-lasting or severe effects …the
term ‘environmental modification techniques’ refers to any technique for
changing—through the deliberate manipulation of natural processes—the
dynamics, composition or structure of the Earth, including its biota …”
However, there is still a need for an open discussion about potential
malicious uses, and military involvement with EGE projects should be avoided
in order to encourage international trust and cooperation.

In response, Dr. B. D. Nagchaudhuri’s, physicist and scientific adviser to the
Indian Ministry of Defence, recommendations were “(A) that research proposals
and projects are available to the public; and (B) that pertinent records
contain clear statements as to why the objective is important, what is the
[Government of India’s] interest, and what is the [United States Government’s]
interest” (American Embassy New Delhi, 1975f) and “ministry officials must be
alerted to any sensitive problems by the technical experts involved”; also,
that “each collaborative project should also be approved at the ministerial or
secretary level of the ministry under which the project would fall i.e. health
projects - Ministry of Health, Agricultural Projects - Ministry of
Agriculture, …This should also hold true whether on the Indian side or the US
side” (American Embassy New Delhi, 1975g). Dr. Hanlon recommends “At the very
least, there should be an open discussion of the [biological warfare]
potential of such projects before they begin, so that countries can make
informed choices” (p. 103 Hanlon, 1975).

There is a value to compartmentalizing different aspects of a government’s
actions. It seems almost self evident that funds for research are best spent
by research agencies, funds for health are best spent in agencies focused on
health, funds for conservation are best spent by agencies trained in and
focused on conversation. Even if there were sufficient funding and resources
we would not want the EPA (Environmental Protection Agency) or DOH (Department
of Health) carrying out military actions; the converse is also true. We don’t
want to rely on our military to carry out conservation, human health, or
humanitarian actions when there are other agencies, without conflicting
priorities, that can and should be doing this (Serafino et al., 2008; Charny,
2016). The author has discussed EGE’s and the ENMOD treaty in person with
current and former members of DARPA, a research branch of the military with an
interest in EGE’s, and has been told that the military has to carry out high
risk (in the sense of new and experimental) research because NSF (National
Science Foundation) and NIH (National Institutes of Health) cannot. I
completely disagree. Research agencies can and should also be funding higher
risk, higher pay-off research instead of abdicating this role to the
military—and to avoid the kinds of conflicts suggested in the WHO experience
in India. This is not done in the US because of historical inertia and
objectively unbalanced federal budget allocations (a Department of Defense,
DOD, estimated research budget of $66 billion versus $29 billion for NIH and
only $6 billion for NSF in FY2015, Hourihan and Parkes 2016). Reallocating
civilian research funds to civilian agencies would also free up the military
to focus on military actions and capabilities.

## Recent experiences with GMO’s in the Indo-Pacific

EGE’s are likely to be initially framed in terms of the GMO (Genetically
Modified Organism) crop debate (Knols et al., 2007).111Although, classical
sterile insect technique involving radiation or chemicals and Wolbachia based
techniques stand as exceptions. These are genetic approaches in the sense that
the organisms chromosomes are affected (Callaini et al., 1997; Robinson,
2005), but they are not considered genetic modifications. Within Hawai‘i,
Rainbow Papaya and GMO Taro serve as contrasting examples of the interaction
between social acceptance, development, and deployment of new technologies.
Carica papaya was not grown in Hawai‘i until after European contact in 1778.
The papaya industry in Hawai‘i was devastated in the 1990’s by the ringspot
virus. A genetically engineered “rainbow” papaya resistant to ringspot
infection was developed at Cornell University by Dr. D. Gonsalves (Ferreira et
al., 2002) who was originally from Hawai‘i. While GMO papaya is not without
controversy (e.g., Harmon, 2014; Hofschneider, 2016) it is credited with
rescuing the industry and is de facto widely adopted in Hawai‘i today (e.g.,
Kallis, 2013).

Colocasia esculenta (Taro or Kalo in Hawaiian) was brought to Hawai‘i by the
ancient Polynesians. A wide range of Kalo varieties have had a central role in
traditional Hawaiian culture as a staple food crop and continues to be
economically important (Whitney et al., 1939; Fleming, 1994). Furthermore,
Kalo is literally the brother of humans (Hāloa) in the Hawaiian creation
tradition and words for family and relationships also refer to parts of the
plant (Kahumoku, 1980). Taro leaf blight (Phytophthora colocasiae) was
introduced to Hawai‘i in the 1900’s and has significantly impacted Kalo
(Nelson et al., 2011). Work at the University of Hawai‘i was begun to to breed
resistant varieties which resulted in patents in 2002. Separately a Chinese
variety of Taro was genetically modified from 2001 to 2006 with a gene from
wheat to be resistant to leaf blight. This resulted in widespread public
outrage and large protest rallies in 2006 that resulted in the university
relinquishing its patents and issuing an indefinite moratorium on the genetic
engineering of Hawaiian Kalo (Ritte and Freese, 2006; College of Tropical
Agriculture and Human Resources, 2009).

With these cases in mind consider a potential EGE project. Culex mosquitoes
were introduced to Hawai‘i in the mid 1800’s. They vector Plasmodium relictum
which is responsible for avian malaria. Many Hawaiian forest bird species,
important in traditional Hawaiian culture (e.g., ‘ahu ‘ula, mahiole, and in
Hawaiian religion), have no immunity or tolerance to P. relictum and have
become extinct, with many currently threatened, as a result (Warner, 1968).
These two previous contrasting examples suggest that genetically modifying
non-native mosquitoes to reduce the frequency of avian malaria is much more
socially acceptable than the reverse: genetically modifying native Hawaiian
birds to be resistant to infection by Plasmodium (although it would be worth
conducting the relevant public surveys to determine this). Also, doing the
research locally in Hawai‘i is not necessarily an advantage in terms of
securing broad local public support, buy-in, and acceptance (however, it is an
advantage in terms of engaging the public).222Another fascinating dimension is
the degree of public awareness and identity with conservation goals and
issues. This varies tremendously across the Indo-Pacific with various emphasis
on terrestrial and marine issues and could be the subject of an article and
research project in its own right. These are aspects that might not initially
be appreciated by scientists designing EGE technologies.

On a broader scale across the Indo-Pacific, consider the cases of golden rice
and Bt-cotton. Rice (Oryza sativa) is a staple crop for a large segment of the
population across the Indo-Pacific. A major nutritional shortcoming of rice is
the lack of beta-carotene that can be metabolized into vitamin A, which in
many of these populations is de facto not simply rectified by supplementing
with additional food sources. This unfortunate situation leads to blindness
and the deaths of over half a million people a year. To address this, rice has
been engineered since 2000 with DNA sequences from other plants to produce
bio-available beta-carotene (Ye et al., 2000; Paine et al., 2005; Tang et al.,
2009). This “golden rice” has also been the target of a great deal of
controversy, protest, and misinformation (e.g., Dobson, 2000; Potrykus, 2001;
Enserink, 2008; Lynas, 2013b). Much of this protest originates in the Western
world where ironically we have a wide range of nutritional supplements added
to our food including vitamin D in milk, calcium in orange juice, niacin and
folic acid in bread, iodine in salt, and fluoride in drinking water. One
question to ask ourselves is, why is it so easy to add all of these
supplements to our food supply, not to mention widespread adoption of
genetically modified corn, soybeans, cotton, potatoes, sugar beets, etc., in
parts of the West, when providing vitamin A in the form of Golden Rice for
much of the world’s population is still not approved and remains in a testing
phase well over a decade later?

Bt-cotton, which has received less attention in the media, provides a
contrasting case to golden rice where a GM crop has been embraced in the Indo-
Pacific and this has been in large part driven by local buy-in. Bt-cotton is
engineered to produce a naturally occurring insecticide from a bacteria
(Bacillus thuringiensis). The intention is to kill larvae of the cotton
bollworm (Helicoverpa armigera). A seed company in India led by Dr. D. B.
Desai began selling “Navbharat 151” seed in 1998 with the claim that the
plants did not have to be sprayed with pesticides for bollworm. This proved to
be the case during a large bollworm outbreak in Gujarat in 2001, which raised
questions. It was found that Navbharat 151 plants had a genetic modification
created by Monsanto. The Indian government filed criminal charges against Dr.
Desai, ordered the seed destroyed, and 4,000 hectares of planted fields
burned. Thousands of farmers rallied to support Dr. Desai and block burning
the fields; the Gujarat government refused to carry out the order; the recall
was cancelled, and some farmers saved their own seed for replanting. The
opposite of concerns about using India as a testing ground as discussed in the
WHO mosquito project of the 1970’s (point 2 above) were expressed: ‘How can
something made in the United States, many of them wonder aloud, be unsafe in
India? “I think they grow it in China and other countries,” says Kalidas
Patel, who grew Navbharat cotton in Gujarat’ (McGray, 2002). Later Monsanto
was granted a license to market Bt-cotton in India and in all likelihood the
prior experience with Navbharat 151 promoted public buy-in (Menon, 2001;
McGray, 2002). In recent years Bt-cotton is widely adopted, approximately 90%
of the cotton grown in India, and a black market for Bt-cotton seeds also
appears to be thriving (e.g., Kathage and Qaim, 2012; Nemana, 2012). However,
this is in no way a simple matter and debates regarding Bt-cotton, Monsanto,
and regulation continue (e.g., Anonymous, 2016; Basheer, 2016). Regardless,
the support among Indian farmers for Bt-cotton stands in stark contrast to the
protests over golden rice being planted in test beds in the Philippines
(Lynas, 2013a). The cause of the difference between these experiences is hard
to isolate and a large number of idiosyncratic effects likely contribute
including the pivotal actions of a few or a single individual. However, the
effects of local buy-in, combined with local access to technologies, and first
hand experience with these technologies, should not be ignored.

Finally, concerns about ecological effects of EGE’s are associated with strong
opposition to the technology (Ernst et al., 2015). There are also questions of
possible, but unlikely, bioaccumulation of toxic proteins and allergenicity
(Curtis, 2007; Reeves et al., 2012). In addition to the four guidelines in the
previous section, despite limited time and funding, we should conduct the work
to have the data on hand to address these questions to the public (Curtis,
2007).

## Everyone has a role to play

We live in a world that is often overly self-polarizing. I am a geneticist; I
entered this field because of personal interest, excitement, and challenges of
the promise and potential of genetics. Unintentionally, this has become a part
of my identity. When I was first exposed to protests over genetic technology
it was all too easy to feel that it was also a personal attack. This is nested
within the context of broader anti-scientific popular views related to climate
change, evolution, renewable energy, vaccinations, etc. The natural reaction
is to reflexively move in the opposite direction and argue that genetic
technologies are safe, protesters don’t understand the issues, etc. and be
overly dismissive; a position that I may not have had initially. The difficult
but essential step for growth is to try to find a middle ground and synthesize
a path forward (see also National Public Radio, 2013). Right or wrong, no
single perspective can do this on its own and, because of our perspectives, we
are often blind to potential issues apparent to other people. It is easier to
see a potential risk if you are looking for a risk instead of working toward
developing a desired application of a new technology. For example, the
potential of allergic reactions to genetic modifications are real and not to
be dismissed (e.g., Nordlee et al., 1996), and many crops have a strong
cultural significance that many people may not be aware of such as Kalo in
Hawai‘i, discussed above, or maize in Chiapas (Bellon and Brush, 1994; Perales
et al., 2005; Brush and Perales, 2007). As geneticists we are in a unique
position to be able to critically assess potential benefits and risks, once we
perceive them, of genetic technology from a scientific perspective. It is our
responsibility to embrace and communicate this rather than contributing to
destructive polarization. However, it is not our job to be overly encompassing
and give equal weight to all objections; we also must be willing to learn from
past experiences (such as the disastrous effects of the perception of possible
military involvement in the WHO program in India) and to rationally disagree
when we reason this to be the case. For example, despite claims to the
contrary (Séralini et al., 2012), there is no scientific evidence that
herbicide resistant maize is carcinogenic. There is a great deal of
misinformation and misconceptions surrounding who would or would not benefit,
and to what degree, from golden rice (Harmon, 2013). Attitudes regarding GMO’s
are divisive, some are not based on factual evidence and can be labeled as
irrational although this quickly gets complex (Stone, 2010; Lynas, 2013a;
Blancke et al., 2015; Hicks, 2015); regardless, the GMO debate will continue
to prove a rich subject for the analysis of the dynamics of politics, the
media, framing effects, confirmation bias, social identity, information
cascades, etc., for many years to come.

An area that can benefit from improvement is to incorporate this synthesis
earlier into the research and development process. If individuals with
different perspectives were able to directly participate in the design of a
new technology, they could shape the direction in which it develops towards an
outcome that might be more desirable and socially acceptable. (Recall the
effect of personal experience with Bt-cotton and its adoption in India.) Often
the way development of a new technology works is in incremental steps of
design, troubleshooting, and research funding, to consultation and approval
from regulatory agencies, to building the logistics of application and
deployment. Public consultation and asking for acceptance occurs only at the
end of the day, when many steps have been cast and it is more difficult and
time consuming to make fundamental revisions. One possibility is to include
grant support for individuals from the social sciences to be “embedded” in a
biological laboratory in order to fully participate in a laboratory’s research
and conduct their own research about social attitudes, context, communication,
perceptions, etc., both in its own right and as a bidirectional conduit to
facilitate communication, public guidance, and knowledge transfer in the
development of EGE technologies (see Kolopack et al. 2015 for a highly
effective example of community engagement albeit not exactly in the same form
that I am proposing here). The local community can directly participate in the
development of a new technology, possibly facilitating progress in a direction
that is unanticipated by the researchers, funding, and regulatory agencies,
but one that results in a greater positive potential being realized at the end
of the day.

## Conclusion

This Indo-Pacific is geographically isolated, under a burden of infectious
diseases, and is in dire need of protection of its natural world. This creates
an opportunity for positive, highly valued, effective applications of EGE’s.
However, it would be a mistake to ignore the history and social realities
thought the region. To reiterate the eight points from the introduction that
have been expanded upon through this article:

  1. 1.

There is a need to enhance and engage communications in all directions.

  2. 2.

EGE applications should only be pursued if there is a genuine benefit to, and
buy-in from, the local population.

  3. 3.

The potential benefits and risks of EGE’s need to be unambiguously
communicated.

  4. 4.

There needs to be a clear unambiguous discussion of unintended side effects
and potential misuses of the technology.

  5. 5.

Humanitarian goals need to be administered and controlled by humanitarian
organizations and conservation goals need to be administered and under the
control of conservation organizations.

  6. 6.

Proactive research needs to be conducted and the data available to address
common concerns.

  7. 7.

It takes broad perspectives to broadly identify potential promises and
pitfalls of EGE’s.

  8. 8.

An early broad-based community discussion of, and involvement in, EGE
development and applications should occur.

Finally, no matter how “new” a technology or situation seems, there is still
much to be learned from history.

## Ancknowledgements

I thank Áki Láruson, Vanessa Reed, and three anonymous reviewers for comments
on the manuscript. Related work in the Reed lab has been recently supported by
the Hawai‘i Community Foundation, the State of Hawai‘i Department of Land and
Natural Resources, and by the Reed family.

## Appendix A: Types of Evolutionary Genetic Engineering

An important concept that cannot be over-emphasized is the diverse types of
EGE’s and their predicted effects. At the risk of oversimplification, here are
four main types with an important boundary between them.333Another important
type of classification are the types of likely effects and dynamics that occur
when the drive systems are disrupted by mutation, recombination, and selection
and how EGE’s are likely to be converted into different types, but this goes
beyond the scope of this article.

Type 0

Generic genetic modifications not designed to change in frequency over time
using evolutionary principles. In general these are expected to either drift
neutrally (if there is little to no effect) or be removed by natural
selection. For example fluorescent proteins are often used to mark and keep
track of genetic inserts; however, these proteins can have toxic effects
(e.g., Liu et al., 1999; Devgan et al., 2004; Shaner et al., 2004, 2005). This
tends to reduce an organism’s fitness and these modifications are not expected
to persist in the wild over many generations.

Type 1

Deleterious EGE’s that are designed to be transient and removed from the
population. Examples of type 1 include the “killer-rescue” system (Gould et
al., 2008), genetic sterile insect technique (Horn and Wimmer, 2003), and
Wolbachia in cytoplasmic incompatibility population suppression applications
(Laven, 1967; Knipling et al., 1968). These may persist in the wild for a
shorter period of time than type 0 EGE’s.

Type 2

Threshold EGE’s that cannot increase in frequency when very rare but can
increase in frequency and persist indefinitely once a critical frequency point
is passed.

Type 2a

Thresholds that are above a frequency of one half. These include chromosomal
rearrangements (Foster et al., 1972), haploinsufficient induced underdominance
(Reeves et al., 2014) and possibly some forms of maternal-effect
underdominance Akbari et al. (2013).

Type 2b

Thresholds that are below a frequency of one half. This includes Wolbachia
(Hoffmann et al., 2011), some forms of maternal-effect underdominance Akbari
et al. (2013), and some theoretical systems (Davis et al., 2001).

Type 3

Unconditionally driving EGE’s that can invade a population from arbitrarily
low frequencies. These include Medea (Chen et al., 2007), homing endonucleases
(Windbichler et al., 2011), transposable elements (Carareto et al., 1997),
meiotic drive (Cha et al., 2006) and some types of CRISPR systems (Gantz and
Bier, 2015; DiCarlo et al., 2015; Hammond et al., 2015).

In one perspective, the most important distinction is the boundary between 2a
and 2b. This predicts what will happen without human intervention (without
additional releases of modified or unmodified individuals) among multiple
populations within a species due to the forces of migration and selection
(Barton and Turelli, 2011). Type 1-2a will tend to reduce in range and
disappear (although this may take many generations) while type 2b and 3 will
tend to spread and become more established (and this may occur in a small
number of generations for type 3) with the concern that once widespread enough
this may be irreversible. While type 2a systems might be considered “gene
drive” in a broad sense the term is probably more accurate to describe type 2b
and especially type 3 systems (gene drive in the strong sense). The boundary
between 2a and 2b represents a balance between ease of transformation of a
population and reversibility back to a transformation free state—a balance
between safety and efficiency.

Some natural EGE systems in the type 3 category have been shown to be capable
of moving across subspecies and species boundaries, rapidly spreading
worldwide, and lowering the average fitness of a species (e.g., Eanes et al.,
1988; Morita et al., 1992; Hill et al., 2016). The concern of this possibly
happening due to artificial genetic engineering is not a new one (Gould et
al., 2006)). For example, fully functioning transposable elements have been
introduced into various new species in the lab (e.g., Brennan et al., 1984;
Daniels et al., 1989), sometimes with little to no discussion of containment
and possible escape. Fortunately there are methods of building in safeguards
to minimize the chance of unintended spread in the wild (Dafa’alla et al.,
2006; Gokhale et al., 2014).

Additionally, it is important to keep in mind the (sometimes unexpected)
effects of mutations and selection that can change the dynamics of EGE’s. For
example, Y chromosome meiotic drive can be quickly suppressed by sex
chromosome aneuploidy (Lyttle, 1981). Arthropod species have been observed to
rapidly evolve to suppress some effects of Wolbachia (Charlat et al., 2007).
Type 0 EGE’s may drift at some frequency in a population by unintended
contamination (e.g., Gonsalves et al., 2012; Xiao et al., 2016); one concern
that goes beyond this is that genetically engineered disease resistance may be
adaptive, if infection by the disease has a large enough fitness cost, and the
type 0 EGE may deterministically increase in frequency in the wild,
essentially becoming a type 3 EGE (although to date there are not clear
examples of this, e.g., Fuchs et al. 2004). Some of these unexpected effects
can be detected in laboratory experiments and incorporated into the design and
predictions of the EGE.

It is already a challenge to filter out misinformation and misconceptions
regarding genetic modifications. The author realizes that this adds another
challenge; however, the fact is there are various types of EGE’s with a range
of predicted effects regarding how well they can be established in the wild
and how reversible they are. It is appropriate, if possible, for these
dynamics to be considered and to interact with regulatory approval and public
acceptance (Harmon, 2014).

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