Genes 2.0

If gene edit­ing could cre­ate do­mes­tic pigs re­sis­tant to the African Swine Fever (ASF) virus, what value would that have to the swine in­dus­try world­wide?

Successful Farming - - CONTENTS - By Betsy Freese, ex­ec­u­tive ed­i­tor Il­lus­tra­tions by Pâté

With a dev­as­tat­ing ASF out­break in at least 10 prov­inces right now, China is prob­a­bly too busy clean­ing up farms to cal­cu­late. In Scot­land, an­i­mal biotech­nol­ogy pro­fes­sor Bruce Whitelaw, chair of ge­nomics at the Roslin In­sti­tute in Ed­in­burgh, is work­ing on this very re­search. De­tails of the ASF stud­ies are top se­cret, but Whitelaw will say that the re­search is on­go­ing and the ASF virus chal­lenge on the pigs “will hap­pen later this year.” The world is wait­ing.

In the U.S., it’s full speed ahead for gene edit­ing in an­i­mal agri­cul­ture. In Au­gust, the biotech com­pany Re­com­bi­net­ics, based in St. Paul, Min­nesota, re­ceived $34 mil­lion in new fund­ing to speed up re­search and de­vel­op­ment of its gene-edit­ing prod­ucts. The com­pany’s main fo­cus is to im­prove live­stock health and wel­fare and to grow hu­man or­gans in pigs.

Will gene edit­ing be ac­cepted by the pub­lic? “I’m cau­tiously op­ti­mistic that we can move this tech­nol­ogy for­ward with­out re­liv­ing the GMO ex­pe­ri­ence,” says John John­son, chief op­er­at­ing of­fi­cer for the Na­tional Pork Board. “There is a com­mit­ment by in­dus­tries in­volved, as well as aca­demics, to have trans­par­ent con­ver­sa­tions about this. They are not try­ing to hide any­thing. The ap­proach is very dif­fer­ent than it was with GMOs 30 years ago. The trans­parency, di­a­logue, and con­ver­sa­tion may lead us down a path where we can achieve con­sumer ac­cep­tance more read­ily and with more con­fi­dence.”

When asked what gene- edit­ing re­search could pro­duce down the road, Univer­sity of Cal­i­for­ni­aDavis ge­neti­cist Ali­son Van Ee­nen­naam and Mitch Abra­ham­sen, chief com­mer­cial and sci­en­tific of­fi­cer for Re­com­bi­net­ics, gave these 10 pre­dic­tions for the next decade.

More prod­ucts will be on the mar­ket for farm­ers.

Re­com­bi­net­ics al­ready has com­mer­cial deals with Hen­drix Ge­net­ics, DNA Swine

Ge­net­ics, and Se­mex, a Cana­dian dairy AI co­op­er­a­tive. Abra­ham­sen can’t pub­licly talk about all the part­ners they are ne­go­ti­at­ing with, but it is a grow­ing list. “We ex­pect ad­di­tional ac­knowl­edge­ments with com­mer­cial part­ners – both in North Amer­ica and Europe – within the next year,” he says. “Health and wel­fare traits will be de­ployed and avail­able to the en­tire in­dus­try through our com­mer­cial part­ner­ships.”

There is cur­rently one prod­uct go­ing through the FDA reg­u­la­tory process – a gene-edited pig re­sis­tant to the PRRS

(porcine re­pro­duc­tive and res­pi­ra­tory syn­drome) virus. That was de­vel­oped by the Univer­sity of Mis­souri and is be­ing li­censed by Genus.

The work Re­com­bi­net­ics is do­ing with Se­mex to in­tro­duce the polled (horn­less) trait into their elite dairy sire lines, is en­cour­ag­ing, says Van Ee­nen­naam. Other an­i­mal wel­fare ap­pli­ca­tions like pigs that do not re­quire cas­tra­tion and

fur­ther dis­ease-re­sis­tance traits are in the pipe­line. “Whether these come to mar­ket will de­pend upon the reg­u­la­tory re­quire­ments and whether they are com­pat­i­ble with an­i­mal­breed­ing pro­gram de­sign,” she says.

An­i­mal wel­fare will be im­proved.

• Horn­less cat­tle are

here. Se­mex is part­ner­ing with Re­com­bi­net­ics to com­mer­cial­ize the polled trait. “It won’t be the only ge­net­ics com­pany of­fer­ing our so­lu­tion for the de­horn­ing process,” says Abra­ham­sen.

• Swine will be nat­u­rally cas­trated.

“To­day in the mar­ket­place, we have a cas­tra­tion-free swine project,” he says.

• Cat­tle will be nat­u­rally heat-tol­er­ant.

A pro­gram at Re­com­bi­net­ics fo­cuses on im­prov­ing the heat tol­er­ance in both beef and dairy cat­tle. This will al­low im­proved ef­fi­ciency of pro­duc­tion in the trop­i­cal re­gions. “If dairy cows in the trop­i­cal en­vi­ron­ments are heat adapted, we’d see a sev­en­fold de­crease in the num­ber of an­i­mals re­quired to pro­duce the milk we do to­day in those re­gions,” says Abra­ham­sen.

• Cat­tle and swine will be health­ier.

Cat­tle will be free of bovine tu­ber­cu­lo­sis, says Abra­ham­sen. Re­com­bi­net­ics is work­ing with a col­lab­o­ra­tion in Europe. Other pro­grams fo­cus on foot-and-mouth dis­ease, as well as the PRRS virus. “Right now those are the two big ones we can talk about pub­licly,” he says. “There are clearly other dis­eases that have im­pact around the world that would be very amenable to a re­search ef­fort to iden­tify the ge­netic vari­a­tion that pro­vides that re­sis­tance.” ASF is one of those dis­eases.

Live­stock ge­netic qual­ity and pro­duc­tion could soar.

“I’m in­ter­ested in us­ing edit­ing to knock out the germ cell, or testes, of a bull and re­place it with the testes of a much bet­ter ge­netic an­i­mal,” says Van Ee­nen­naam. “You could have a bull that is well suited to your en­vi­ron­ment but is car­ry­ing the ge­net­ics – or just the testes – of the very best bull in the breed. That has a lot of po­ten­tial in de­vel­op­ing coun­tries like Africa, where fa­cil­i­ties aren’t there for re­pro­duc­tive tech­nolo­gies. I call it the sur­ro­gate sire idea. In New Zealand, they are work­ing on it in sheep.”

Traits will be stacked.

“Our goal is to put mul­ti­ple ed­its in an an­i­mal,” says Abra­ham­sen. Think of it as stack­ing traits. “We would have an­i­mals that are horn­less, dis­easere­sis­tant, heat-tol­er­ant, and pro­duce less meth­ane and less waste com­pared with an­i­mals to­day in our pro­duc­tion sys­tems.”

Con­sumers will bet­ter un­der­stand that gene edit­ing is dis­tinct from GMO trans­genic tech­nol­ogy.

How well con­sumers un­der­stand gene edit­ing “prob­a­bly de­pends on who is dis­sem­i­nat­ing the mes­sage,” says Van Ee­nen­naam. Gene edit­ing can ac­tu­ally be used to in­tro­duce DNA from a dif­fer­ent species, so it is not nec­es­sar­ily dis­tinct from trans­genic tech­nol­ogy, she ex­plains. At the same time, it can also be used to make al­ter­ations that ex­actly mimic ex­ist­ing ge­netic vari­ants within a species or spon­ta­neous ge­nomic al­ter­ations.

“None of these is uniquely risky, as demon­strated by decades of GMO safety stud­ies and con­ven­tional breed­ing,” she says. “How­ever, some groups have suc­cess­fully spread fear around GMOs, re­sult­ing in a lu­cra­tive non-GMO la­beled mar­ket. They may also find it to their ad­van­tage to con­flate gene edit­ing with GMO tech­nol­ogy and con­tinue to mon­e­tize that fear-based mes­sag­ing around gene edit­ing.”

Reg­u­la­tory agen­cies will con­tinue to reg­u­late the safety of gene-edited prod­ucts.

Hope­fully, they don’t con­tinue to reg­u­late the process it­self if the re­sult­ing prod­uct is in­dis­tin­guish­able from a nat­u­ral prod­uct, says Abra­ham­sen. “The fo­cus is on ac­cel­er­at­ing the nat­u­ral breed­ing process. We iden­tify the ge­netic vari­a­tion that con­trols wel­fare and health traits, and then we in­crease the fre­quency of that vari­a­tion within our elite, ef­fi­cient an­i­mals.”

The USDA reg­u­lates gene-edited plants with the ap­proach that if the plant con­tains no novel DNA and could have been pro­duced us­ing con­ven­tional breed­ing, then it is not sub­ject to ad­di­tional reg­u­la­tion. In the case of edited an­i­mals, the FDA is in charge. It is ask­ing for a pre­mar­ket “new an­i­mal drug” ap­proval

ap­pli­ca­tion for all in­ten­tional ed­its in food an­i­mals, says Van Ee­nen­naam. “It is dif­fi­cult to un­der­stand what po­ten­tial risks from edit­ing an­i­mal genomes might war­rant such a high reg­u­la­tory bar, con­sid­er­ing al­ter­ations that could have been ob­tained us­ing con­ven­tional breed­ing – such as polled dairy cat­tle.”

In­ter­na­tional ac­cep­tance to gene edit­ing will grow.

In Au­gust, Ja­pan an­nounced that it con­sid­ers a ge­need­ited an­i­mal no dif­fer­ent than a nor­mal an­i­mal in the food chain, says Abra­ham­sen. South Amer­ica has ap­proved ge­need­ited an­i­mals. Canada reg­u­lates the process based on whether the prod­uct is novel or not. “These coun­tries are reg­u­lat­ing the prod­uct – not the process,” he says.

Whether other coun­tries ac­cept gene edit­ing is com­pli­cated, says Van Ee­nen­naam. “There is no con­sis­tency or even sci­ence­based ra­tio­nale to trig­ger reg­u­la­tion. It ap­pears al­most ar­bi­trary. Given the lack of reg­u­la­tory har­mony among coun­tries, it is al­most im­pos­si­ble to pre­dict in­ter­na­tional ac­cep­tance. Rather, it is likely there may be trade dis­rup­tions and fraud, be­cause many ed­its can­not be de­tected.”

Farm­ers will con­tinue to sup­port the tech­nol­ogy.

Farm­ers are on board, says Abra­ham­sen. “When Se­mex an­nounced its deal with us, it re­ceived pos­i­tive feed­back from co-op mem­bers.” Ten years from now, farm­ers will ac­cept the in­no­va­tions even more than they do to­day, he pre­dicts.

“Farm­ers are very prag­matic and busi­ness­minded,” says Van Ee­nen­naam. “If a tech­nol­ogy helps ad­dress a prob­lem in a cost-ef­fec­tive way, they will adopt it.”

Govern­ment fund­ing for re­search may be dicey.

Re­com­bi­net­ics gets some fund­ing from the USDA and FFAR (Foun­da­tion of Food and Agri­cul­ture Re­search), which funded the com­pany’s cas­tra­tion-free pro­gram, but the con­flict be­tween USDA and FDA reg­u­la­tions has hurt the in­dus­try, says Abra­ham­sen.

If reg­u­la­tions in­volve a “new an­i­mal drug” ap­proval for ev­ery edit, this will con­fine com­mer­cial de­vel­op­ments to large com­pa­nies, says Van Ee­nen­naam, ef­fec­tively shut­ting out the pub­lic sec­tor and small com­pa­nies. “This hap­pened with ge­netic en­gi­neer­ing. It makes lit­tle sense to de­velop ap­pli­ca­tions that can­not ever be com­mer­cial­ized.”

Bio­med­i­cine so­lu­tions for hu­man health will boom due to gene-edited live­stock.

Re­com­bi­net­ics has two busi­ness units out­side agri­cul­ture. One is fo­cused on us­ing pigs as mod­els for hu­man dis­ease re­search. The phys­i­ol­ogy and me­tab­o­lism of a pig (vs. a mouse) is more sim­i­lar to a hu­man, says Abra­ham­sen. “Our an­i­mal mod­els will al­low us to pre­dict and iden­tify those changes that hap­pen be­fore the dis­ease ap­pears. We’ll un­der­stand which an­i­mals will get the dis­ease and which an­i­mals won’t.”

For ex­am­ple, the com­pany has de­vel­oped pigs with high blood pres­sure. “We should be able to iden­tify biomark­ers that in­di­cate be­fore the high blood pres­sure in­creases, that these an­i­mals are the ones that will need ther­apy,” he ex­plains. “We can de­velop pre­ven­tive medicine vs. treat­ment medicine.”

The sec­ond bio­med­i­cal unit is fo­cused on re­gen­er­a­tive medicine. “We use pigs as ‘oinku­ba­tors’ to pro­duce hu­man cells, tis­sues, and or­gans,” says Abra­ham­sen. Within six years, he pre­dicts, the com­pany will pro­duce hu­man cells and tis­sues that will ad­dress is­sues with blood short­ages, stor­age of blood prod­ucts, di­a­betes, and liver dis­ease.

“Ul­ti­mately, in the next 10 years, we will de­velop hu­man or­gans for trans­plant, specif­i­cally with a fo­cus on cornea, heart, kid­ney, and liver,” he says.

Else­where, Har­vard Univer­sity ge­neti­cist Ge­orge Church is us­ing gene-edit­ing tech­nol­ogy to cre­ate pigs that are free of harm­ful viruses, an im­por­tant step to­ward trans­plant­ing pig or­gans into hu­mans.

Even the world’s largest pork pro­ducer, Smith­field Foods, has es­tab­lished a bio­science unit in the hopes of grow­ing pig or­gans that could one day be trans­planted into hu­mans.

The world is wait­ing.

Farm­ers are very prag­matic and busi­ness-minded. If a tech­nol­ogy helps ad­dress a prob­lem in a cost­ef­fec­tive way, they will adopt it.

Ali­son Van Ee­nen­naam

Mitch Abra­ham­sen

Newspapers in English

Newspapers from USA

© PressReader. All rights reserved.