This pgEd lesson aims to examine how genome
editing technologies, with a focus on CRISPR,
might be used to address the environmental
issues we are facing.
To explore how genome editing could impact
our environment, we will discuss 3 case studies.
The first case study is on agriculture, where
we will see how genome editing might be used
to lower the toxicity of an important food
crop - cassava.
Next we will discuss an insect-borne diseases
case study, where we will see how genome editing
might be used to engineer mosquitoes to prevent
them from infecting Hawaiian honeycreepers
with avian malaria.
Finally we will explore how genome editing
might be used to bring back the woolly mammoth
in our de-extinction and permafrost preservation
case study.
But first things first: what is genome editing?
Genome editing is a type of genetic engineering,
used for making specific, targeted changes
to an organism’s own DNA. One of the genome
editing techniques that has generated the
most excitement, due to its efficiency and
ease of use, is called “CRISPR”.
Originally discovered in bacteria, CRISPR
is now being used as a tool with applications
in many areas, including medicine, agriculture,
and the environment. For more information
on the use of CRISPR and related genome editing
tools in human health, please see pgEd’s
lesson plan Genome Editing and CRISPR.
To introduce the first case study on cassava,
we would like people to consider the following
scenario:
You live in a rural village and your relatives
are suffering from Konzo, a disease that causes
paralysis. You rely on a plant called cassava
as your main source of food. Cassava naturally
produces a toxin. At high concentration, this
toxin can make people sick with Konzo. However,
soaking the cassava in water for a couple
of days before eating it prevents this problem.
Scientists have proposed to genetically alter
the cassava plant to make it less dangerous.
You wonder whether providing a clean source
of water, such as a well, to your village
could be a better solution. What are the questions
you have for the scientists about their plan?
You may want to pause here to think about
your own answers to these questions.
Answers to this question vary, but typically
include questions along the lines of:
What if the genetic alteration makes cassava
less safe?
Will the alteration of the cassava plant truly
fix all the Konzo-related problems that the
villagers are facing?
Will people who are already poor be asked
to pay for the altered cassava plant seeds?
Cassava is an important crop for over 800
million people worldwide. It is a high-calorie
food that can grow in nutrient-poor soil and
tolerate drought. Increasingly, the use of
cassava is gaining popularity across the world
- you may be familiar with cassava products
such as tapioca or the “bubbles” in bubble
tea or “boba”.
Cassava plants naturally produce a toxin that
can cause Konzo, a disease that leads to paralysis
and can potentially be deadly. This is particularly
problematic when cassava is grown in drought
conditions. However, there are different approaches
for avoiding Konzo. First, soaking cassava
in water for several days reduces the plant’s
toxicity. Second, eating a protein-rich diet
can help the body to break down the toxin
more effectively. While these solutions may
appear to be relatively simple, their implementation
can be difficult due to systemic and historical
barriers. In parts of Africa where Konzo is
prevalent, for example, European colonialism
has left behind extreme poverty. Access to
water and protein-rich foods is scarce, and
people who are affected by paralysis are often
not able to make the trip to the nearest river
or well to collect the water needed for soaking
the cassava. Moreover, waiting several days
to soak cassava is not possible for people
who are urgently hungry. This is why Konzo
is considered a disease of poverty. Furthermore,
Konzo maintains the cycle of poverty, as people
with the disease lose the ability to work
and collect water.
So how might genome editing help improve health
and reduce disease for the people who rely
on cassava?
There are two genes that are responsible for
the toxicity of cassava. Scientists have proposed
using CRISPR to make specific changes to these
genes with the goal of reducing the plant’s
toxicity. One major advantage of using CRISPR
is that it is much faster than traditional
breeding methods. Furthermore, CRISPR technologies
can be applied to local varieties of the cassava
plant, thus maintaining characteristics of
the plant that make it well-suited to the
region where it will be grown.
Scientists and communities are considering
the risks and benefits of using genome editing
to lower cassava toxicity. For example, the
cassava’s toxicity appears to be correlated
with its ability to tolerate drought, as the
drier the circumstances are, the more toxin
the plant produces. Could the edits negatively
affect the plant’s drought-tolerance, which
is a beneficial trait for growing in many
regions across the globe? Furthermore, cassava’s
toxicity is thought to provide a defense against
insects. Could the edited cassava plants require
farmers to use pesticides in order to grow
their crop? And lastly, what will the economic
implications be? Who will own the plants as
well as the seeds of the edited cassava? Will
farmers be able to afford this new crop?
Stepping back further, Konzo is a disease
of poverty with lack of access to water and
protein-rich food being the main contributors.
Should disease prevention efforts focus on
a genetic solution? Or should the focus be
on breaking the cycle of poverty that is at
the root? Or maybe a combination of approaches
is the best way forward? While genome editing
offers a possible solution to this problem,
careful consideration is needed to determine
if it is the best solution and whether the
potential benefits outweigh the risks.
As an introduction to the second case study,
please consider the following scenario:
You are a scientist. You are visiting an island
where a species of birds is in danger of extinction
because they suffer from a disease that is
given to them through mosquito bites. You
think that the best way to rescue the birds
is to use genome editing to wipe out the mosquitoes
on the island.
You know that the people who live on the island
need to be partners in this project. How do
you establish such a partnership? What is
the information you need to gather from them,
and what is the most important information
for you to share? What are you looking to
learn?
You may want to pause here to think about
your own answers to these questions.
Typical responses that we hear about establishing
a partnership include: setting up a lab in
the affected area, hiring staff from the island
who can provide local expertise, and hosting
a series of meetings to have dialogue with
the general public.
With regards to information exchange and who
to include in conversations, people typically
recognize that engaging local communities
is important from an ethical point of view
to build trust between scientists and the
public and to ensure informed consent for
projects going forward in their environment.
Furthermore, community partnerships can bring
to the table diverse types of local knowledge,
which can lead to the development of better
strategies for addressing the problem at hand.
Hawaiian honeycreepers are colorful birds
that are culturally important to the Indigenous
people of Hawaii. They are at risk of extinction,
in part because their habitat is being destroyed
by human activity. Another threat to the survival
of these birds are mosquitoes that carry an
avian form of malaria. Avian malaria is a
bird disease caused by parasites that spread
to the honeycreepers through mosquito bites.
Since the introduction of mosquitoes and avian
malaria to the Hawaiian Islands in the 1800s,
honeycreepers have been forced to live at
higher altitudes where the temperatures are
too low for the mosquitoes to survive. However,
to gather food, the birds have to travel into
the valleys, where they are at risk of malaria
infection. With average annual temperatures
increasing in Hawaii, mosquitoes are now able
to survive at higher and higher altitudes.
This is shrinking the honeycreepers’ habitat
even further and bringing them to the brink
of extinction.
So how might genome editing help prevent the
Hawaiian honeycreepers from going extinct?
Editing the DNA of mosquitoes could be used
to prevent them from infecting Hawaiian honeycreepers
with avian malaria. One suggested approach
is to introduce a genetic trait in the mosquitoes
that would greatly reduce and possibly fully
eliminate the mosquito population. A second
approach is to introduce a genetic trait in
the mosquitoes that would make them unable
to carry the avian malaria parasite, so they
can no longer transmit the parasite to the
honeycreepers.
The challenge of introducing these genetic
traits into the population of mosquitoes living
in the wild is that, under normal sexual reproduction,
the trait will only be passed to ~50% of the
next generation. This means that the trait
would not spread very widely in the Hawaiian
mosquito population.
To address this problem, a genetic technology
known as a “gene drive” could be used
to increase the likelihood that a genetic
trait will be passed to the next generation.
In this way, a gene drive allows for a specific
trait to quickly spread in a population. With
the advent of CRISPR, the gene drive approach
has become a practical reality.
So let’s have a look at some of the major
questions and considerations with regards
to using genome editing to prevent the extinction
of the Hawaiian honeycreeper.
First off: Which genetic trait would be the
most beneficial to introduce into the wild
mosquito population? One that would greatly
reduce and possibly eliminate the mosquito
population? Or one that would prevent the
mosquitoes from carrying the avian malaria
parasite?
Given that the mosquitoes are not native to
Hawaii, wiping them out could be considered
as a “reset button” - one that would also
prevent these mosquitoes from transmitting
other diseases to wildlife as well as humans.
However, what if the mosquitoes have become
an integral part of the ecosystem during the
~200 years that they have been present in
Hawaii? What if other species are now dependent
on the mosquitoes for their survival?
Another consideration is whether the gene
drive could have far-reaching effects? For
example, a gene drive targeted to wipe out
the local mosquito population in Hawaii could
end up driving this species to extinction
across the globe. Because of this, scientists
are trying to design built-in safety mechanisms
to limit the effects of the gene drive to
the target species, or even to reverse the
gene drive if unintended consequences arise.
As different approaches are being considered
to prevent the Hawaiian honeycreepers from
going extinct, the worthwhile benefits as
well as the reasonable risks need to be weighed.
These are questions that require strong partnerships
with communities to gather diverse expertise
- such as knowledge of local entomology and
epidemiology as well as local social structures
and politics.
As an introduction to the third case study,
please consider the following scenario:
You are a farmer in Siberia, tending animals
and vegetables on your land. You heard a team
of scientists are hoping to bring the woolly
mammoth back from extinction. These animals
once roamed exactly where you live. How do
you feel about this plan? What are your questions
about it?
You may want to pause here to think about
your own answers to these questions.
The responses we typically get to this scenario
range from excitement about the idea that
the display of a woolly mammoth that someone
might have seen in a natural history museum
might come to life - to skepticism about the
intent of this project - and concern about
the possibility that Indigenous people living
in areas of the world where woolly mammoths
used to roam (such as Siberia, Alaska, Canada,
and Greenland) are not part of the decision-making
process and stand to lose more and more of
their land.
The scenario on the previous slide describes
the idea of de-extinction. De-extinction is
the process of reviving an extinct species
or creating an organism that resembles an
extinct species. Genome editing tools have
made this a possibility that some people are
interested to consider - and the animals shown
on this slide are all currently the focus
of various de-extinction projects.
One of the reasons mammoths are being considered
for de-extinction is the potential role they
could play in slowing the thawing of permafrost.
The permafrost is a layer in the ground that
remains below 32ºF (0ºC) for at least two
years in a row. Permafrost is found in areas
where the average temperature rarely gets
above freezing - on land as well as below
the ocean floor. As average global temperatures
rise, the total area of permafrost is shrinking.
Thawing of the permafrost is a particular
concern because the frozen soil stores significant
amounts of carbon. This carbon is released
in the environment in the form of carbon dioxide
and methane, two greenhouse gases that trap
infrared radiation near the Earth’s surface
and therefore could accelerate the rise of
average temperatures around the globe.
Furthermore, in regions such as Alaska (where
85% of the land has permafrost), the infrastructure
is increasingly affected as the solid frozen
foundations disappear.
And considering that permafrost is thought
to contain frozen and preserved bacteria and
viruses - the concern is that these pathogens
might revive when the permafrost melts and
could thereby introduce diseases into the
world for which we have no natural defenses
or treatments.
So how might thawing permafrost be slowed
or perhaps even reversed?
One idea to protect the thawing permafrost
is to undertake a massive effort to return
the current tundra and taiga landscapes of
the Northern Hemisphere to grasslands that
used to cover this region thousands of years
ago.
During the short summer, grasslands keep the
ground cooler as their light color reflects
sunlight more effectively than the dark-colored
shrubs and trees of the tundra and taiga,
respectively.
During winters, large herds of grazers (such
as deer, horses, and bison) in the grassland
biome keep the ground cooler. Grazing herds
of herbivores disrupt the snow cover as they
look for food underneath. This compaction
and removal of snow exposes the ground below
to the cold winter air, which prevents the
permafrost from thawing and may even expand
this frozen layer.
To test the idea that recreation of these
grasslands could prevent thawing of permafrost,
researchers have gathered a number of grazing
animals (such as elk, musk oxen, and reindeer)
in a 5,000-acre reserve called the Pleistocene
Park in Siberia. Preliminary data suggest
that this effort does indeed lower the ground’s
temperature and slows the thawing of the permafrost,
keeping more of the greenhouse gases trapped
in the frozen soil.
While encouraging, this effect would need
to be translated on a larger scale to combat
the thawing of permafrost globally. Large
herds of big grazers would be needed to disrupt
the mossy tundra and forested taiga landscapes
and recreate the grassland biome of the past.
And a key animal in this landscape was the
woolly mammoth.
Could de-extinction of large woolly mammoth
herds recreate the vast grasslands of the
past and help to preserve the permafrost?
A leading strategy in the de-extinction of
woolly mammoths is using CRISPR to introduce
some genetic traits from woolly mammoths into
the DNA of its close relative, the Asian Elephant.
In other words, the goal of the woolly mammoth
de-extinction project is to create a cold-resistant
“woolly” elephant, sometimes called a
“mammophant”.
Though a number of technical hurdles remain,
this project was able to get underway because
of three things:
1) the discovery of preserved mammoth DNA;
2) the existence of a close living relative of
the mammoth, the Asian elephant;
and 3) the availability of genome editing tools,
such as CRISPR.
By analyzing preserved mammoth DNA, scientists
have been able to identify genes that are
responsible for key traits that helped the
mammoths survive in cold climates. These traits
include longer hair, more fat under the skin,
and a circulatory system adapted to cold temperatures.
Using CRISPR, researchers are introducing
these traits into Asian elephant cells in
a laboratory setting. This is possible because
Asian elephants and woolly mammoths are closely
related, sharing 99.96% of their DNA. To make
a mammophant, hundreds or maybe thousands
of genome edits are likely needed.
Still, if this project is to go forward, several
steps and challenges lie ahead. Once the Asian
elephant cells have been edited (thus creating
mammophant cells), these cells could then
be used to generate a mammophant embryo. That
embryo could then be transferred into the
uterus of an Asian elephant, with the goal
of starting a pregnancy that would give rise
to a baby mammophant.
The mammoth de-extinction project is very
much in its infancy. Besides some of the technical
challenges discussed in the previous slide,
there are a number of ecological and ethical
questions to consider as well.
First of: Is it acceptable to use the Asian
elephant, an endangered species, in this project?
There could be risks to an animal used as
a surrogate to carry a mammophant pregnancy.
Researchers working on this project have suggested
the use of an artificial womb to eliminate
the surrogacy issue; however, this technology
is still in its infancy and could not yet
support the development of a mammophant to
term. Further concerns exist around the use
of Asian elephants in raising the mammophants
after they are born. Elephants are very social
animals, and the social effects of this project
on both the Asian elephants and the mammophants
are unknown. For example, how would we ensure
appropriate rearing and socialization of the
mammophants, which will provide them with
the necessary skills to live in mammophant
herds and survive cold climates? How would
the Asian elephant herd be affected when baby
mammophants are introduced? Or when those
mammophants are subsequently removed from
the herd to inhabit colder Northern climates?
However, this project may also yield unexpected
benefits for preserving the Asian elephant.
When scientists working on the mammoth de-extinction
project heard about a strain of herpes virus
that is deadly for Asian elephant calves,
both in captivity and in the wild, they began
an effort that may lead to a cure for this
disease.
Another important question is: where would
the newly de-extincted animals live? There
are people currently living in the tundra
and taiga landscapes where the mammophants
are suggested to be introduced. How will their
voices be weighed in this discussion – specifically,
the voices of Indigenous peoples in these
regions who, throughout history, have seen
their claims to land being stripped away?
And if mammophants are introduced, how would
they impact the local ecosystems? There are
some examples of success when an animal is
reintroduced to its habitat. However, given
that mammoths have been extinct for several
thousands of years, it is hard to know what
impact they might have. Should we proceed
when the consequences of introducing newly
revived species into wild ecosystems might
have outcomes that are hard to predict?
And lastly: do we have an obligation to try
any and all efforts to prevent thawing of
the permafrost even if those efforts are expensive,
have a high risk of failure, could disrupt
existing ecosystems and biomes, or require
the use of endangered animals? How do we balance
the risks of proceeding with this project
with the risks of not proceeding, if there
is a chance, however small, that the mammophants
could play a role in preventing the release
of carbon from the permafrost?
Throughout this lesson we have explored various
ways in which genome editing technologies
might be used to address the environmental
issues we are facing.
The case studies show how genome editing technologies
may hold promise for solving health and environmental
problems, but they also highlight some of
the complex ethical and ecological perspectives.
As risks and benefits are weighed, the need
for strong partnerships with the communities
that are impacted by the work is key in gathering
the diverse expertise that is required for
developing a successful strategy for the problem
at hand.
