Can Genetic Engineering Save the ‘I‘iwi? Scientists in Volcano Weigh the Odds

posted in: Climate Change, March 2020 | 0

Temperatures are rising. And as they soar, so, too, do the mosquitoes that carry the parasite that causes avian malaria, fatal to so many of the native Hawaiian forest birds.

For years, scientists and biologists concerned with the health of forest bird populations have struggled to address the problem of avian malaria, a major factor in wiping out most native birds from lowland forests. But now, as the impacts of global warming accelerate, the forests that have become refugia for ‘i‘iwi and other native birds that are extremely vulnerable to malaria are in danger of losing that status. Warmer conditions will allow mosquitoes to invade mid- and high-elevation forests, resulting in the spread of malaria infection to the last remaining populations of many of the most threatened bird species on the planet.

To address this, current approaches include reducing mosquito habitat through fencing and the removal of feral animals that create wallows where mosquitoes can breed and efforts to infect male mosquitoes with a strain of the Wolbachia bacterium that makes them infertile when they mate with females in the wild.

But what if the birds could be made resistant to malaria through genetic engineering?

That was the question that scientists from the University of Wisconsin- Madison and the U.S. Geological Survey’s Pacific Island Ecosystems Research Center in Volcano addressed in research that they described in a paper published in the journal Biological Conservation in January.

The scientists – Michael Samuel and Wei Liao, from Wisconsin, and Carter T. Atkinson and Dennis A. LaPointe from the USGS – simulated what might occur if ‘i‘iwi (Drepanis coccinea) that had been genetically engineered to resist malaria were released into wild, non-resistant populations. Although ‘i‘iwi are highly sensitive to malaria, with more than 90 percent of those infected succumbing to the disease, they are still relatively abundant on the Big Island.

The computer models assumed that one of the chief obstacles – the development of a population of ‘i‘iwi that do not just tolerate malaria, but are actually able to resist infection – was an accomplished fact and that this trait would be passed on to offspring. (The authors noted that even if malaria-tolerant ‘i‘iwi populations could be established, the birds would still serve as “an important disease reservoir for other Hawaiian species that currently exist only in high elevations with low malaria risk.”)

Simulations were run to look at the effect of the release of these resistant birds into the wild at various times and in various numbers under three climate change scenarios, as modeled by the Intergovernmental Panel on Climate Change. “We are just working through all the options that are out there,” LaPointe said as he and Atkinson discussed the article in an interview last month with Environment Hawai‘i. Both took pains to stress that they were not recommending this as an option, but rather just putting it out there for consideration.

With all the recent advances in genetic engineering that have occurred over the last couple of years, LaPointe added, he and his co-authors were exploring what might be required if it were possible to “modify an organism to save it from the brink of extinction.

“Could we find, or could we modify, a honeycreeper so that it is actually resistant to malaria, and not just tolerant? And if we could do that, is there time to put it in the environment and actually have it propagate through the environment and rescue the birds from an otherwise certain path to extinction?”

The article, “Facilitated adaptation for conservation – Can gene editing save Hawai‘i’s endangered birds from climate driven avian malaria?” – concludes that this “may be a useful alternative or additional strategy if control of malaria transmission by mosquitoes is not suc- cessful or proves too costly.”

As recently as 2017, the same four authors – Liao, Atkinson, LaPointe, and Samuel – suggested that mosquito control strategies could be the best way to ward against malaria transmission at high elevations and, combined with other approaches, help protect native birds at mid-level elevations. (See their paper, “Mitigating Future Avian Malaria Threats to Hawaiian Forest Birds from Climate Change,” PLOS/One, January 6, 2017.)

To date, however, research into mosquito control on a landscape scale – the scale needed to meaningfully address the threat of avian malaria – has not borne fruit. Since 2016, the state has supported efforts to infect Culex quinquefasciatus mosquitoes, which carry the malaria parasite to birds, with a variety of Wolbachia bacteria that will make the males infertile with wild female mosquitoes and suppress wild populations if sufficient numbers of males are released. A related approach with Aedes mosquitoes is being used in other parts of the world, but with these mosquitoes, infection with a new strain of Wolbachia can actually prevent the mosquitoes and their offspring from transmitting human pathogens such as the Dengue virus. Whether something similar could occur with Culex and avian malaria is still unknown. Despite additional funding in 2017 and 2018 from both state and federal agencies, “the project still did not result in the development of a Wolbachia infected C. quinquefasciatus mosquito, due to the complexity of methodologies and technical specialization required for such an undertaking,” according to a report on the project submitted to the Legislature by the state Department of Agriculture in December.

But in any case, if genetically modified ‘i‘iwi resistant to malaria are able to be developed and then released in sufficient numbers to mate with wild birds, mosquito control would actually work against the goal of developing a malaria resistance in the wild population.

Absent the malaria-carrying mosquitoes, the resistant ‘i‘iwi would have no evolutionary advantage. That is, non-resistant birds are just as likely to survive and reproduce as the resistant ones. To ensure that the genetic ability to resist malaria becomes dominant over time, sufficient selection pressure favoring resistance – in the form of disease – needs to be present. No mosquitoes means no such pressure.

For now, though, said LaPointe, “the focus is on mosquito control with existing technology… In 20 years, if we find that that doesn’t work, and the technology exists for developing a resistant ‘i‘iwi and it’s acceptable to the public, then is this” – release of malaria-resistant ‘i‘iwi – “an option, at that time?”

Under the scenarios described in the Conservation Biology article, however, the sooner the release of resistant birds occurs at mid-elevation forests, the better. “When releases of resistant ‘i‘iwi were 3 birds per square kilometer (1,311 total birds during 1-2 years) between 2030 and 2050,” the authors write, “we predicted high population levels (more than 800 ‘i‘iwi per square kilometer) of malaria-resistant ‘i‘iwi could be established by 2100” under the most dire climate model (RCP8.5).

“Overall earlier release of more resistant birds in mid-elevation forests meant that ‘i‘iwi populations recovered sooner and achieved higher population levels. Resistant ‘i‘iwi dominated the total ‘i‘iwi population within 20 to 30 years after release and were more abundant than the predicted ‘i‘iwi density without the release of resistant birds,” they found.

Another option considered in the paper was that of releasing resistant ‘i‘iwi on islands such as O‘ahu, where the natural populations have been severely reduced or have died out altogether. “You could establish a population on an island where there are currently no birds, so you could generate enough birds in the wild, and then be able to draw birds from that island when you’re ready to release them on the other islands,” Atkinson said.

The authors simulated population growth of resistant ‘i‘iwi after the release of 30, 40, or 50 birds in an area where ‘i‘iwi are no longer found: “Our results showed that populations of more than 2,000 malaria-resistant ‘i‘iwi could be achieved within 30 years of introduction from the release of 30 birds and somewhat sooner for initial releases of 40 or 50 birds.”

The development of a resistant ‘i‘iwi is still a moon shot, they both admitted. When he was approached about the idea, Atkinson said, “I was kind of incredulous about the whole idea of genetically engi- neering a bird that is resistant to malaria. It will be extremely difficult to do. The immune response to malaria is so complicated. We don’t really understand exactly how it works even in human malaria. To think you can modify maybe one gene to make a bird resistant or refractory is being really optimistic.”
Even if all the technical obstacles can be overcome, there remains the matter of possible cultural resistance. “The application of gene editing to conserve wildlife populations is a controversial issue,” the authors observe, although in the case of last-ditch efforts to save high-value endangered species, public acceptability is “significantly higher.”

“In traditional Hawaiian culture, native plants and animals are often viewed as the manifestation of gods or ancestral spirits,” they note. “Proposed genetic modification of the Hawaiian staple crop, taro, met with such resistance from Hawaiian cultural practitioners that a statewide ban was enacted in 2009. ‘I‘iwi and many other native forest birds may be ‘aumakua, family gods, or spiritual guardians and as such would be considered sacred. Consideration of the traditional beliefs of Hawaiians would be an important first step before any genetic modification of ‘i‘iwi is attempted.” Even assuming that cultural considerations are satisfactorily addressed, how likely is it that the technical competence to develop a malaria-resistant ‘i‘iwi will be achieved and a sufficiently large captive population will be developed and released in time to save the species?

“I tend to be pessimistic about that, that it’s going to be anytime soon. I don’t think I’ll be around to see it if it happens,” LaPointe said. “But the pace of these things is unpredictable in my mind. All it takes is identifying the right gene and somebody who wants to invest in the effort.”

“Malaria is a really difficult problem to solve,” Atkinson added. “People have been trying to develop a malaria vaccine for over 50 years and we still don’t have anything that is completely effective. The parasite is well adapted to evading the immune system.”

—Patricia Tummons

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