Strate­gies for re­spon­si­ble gene edit­ing

Financial Mirror (Cyprus) - - FRONT PAGE -

The dis­cov­ery of a pow­er­ful new tool ca­pa­ble of ad­dress­ing health and en­vi­ron­men­tal prob­lems as di­verse as malaria, Lyme dis­ease, and in­va­sive species should be a cause for cel­e­bra­tion. But, be­cause the tool, called CRISPR, can al­ter en­tire pop­u­la­tions of wild or­gan­isms (and thus shared ecosys­tems), en­sur­ing that th­ese in­ter­ven­tions are de­vel­oped re­spon­si­bly poses an un­prece­dented chal­lenge for sci­ence and so­ci­ety.

Hu­mans have been al­ter­ing an­i­mals and plants through selec­tive breed­ing for mil­len­nia; but, be­cause th­ese changes typ­i­cally re­duce the ca­pac­ity for sur­vival and re­pro­duc­tion in the wild, they do not spread to wild pop­u­la­tions. Al­ter­ations ac­com­plished us­ing CRISPR, which en­ables sci­en­tists to edit a cell’s DNA with un­prece­dented pre­ci­sion, are dif­fer­ent in one cru­cial re­spect: The process can re­sult in “gene drive,” a nat­u­rally oc­cur­ring fea­ture of some genes that en­ables them to spread through a pop­u­la­tion over gen­er­a­tions, even if they do not help sur­vival (and thus re­pro­duc­tion).

Sim­ply put, we can now con­tem­plate al­ter­ing wild pop­u­la­tions in very spe­cific and con­se­quen­tial ways. Those changes can be highly pos­i­tive. By al­ter­ing cer­tain fea­tures of mos­qui­toes, we could re­duce or even erad­i­cate an­cient scourges such as malaria and dengue that af­flict hun­dreds of mil­lions of peo­ple each year. (Malaria alone kills a child ev­ery 90 sec­onds, on av­er­age.) By per­ma­nently im­mu­nis­ing the rel­e­vant an­i­mal pop­u­la­tions, we could pre­vent new cases of Lyme and other dis­eases that orig­i­nate in wild or­gan­isms, or we could block newly emer­gent pathogens such as the Zika virus, which has been linked to an epi­demic of stunted brain de­vel­op­ment in new­borns in Latin Amer­ica.

As for the en­vi­ron­ment, hu­man ac­tiv­i­ties have al­ready im­pacted ev­ery ecosys­tem on Earth, with far-reach­ing con­se­quences – for us and many other species – many of which are yet to un­fold. Gene drive el­e­ments could po­ten­tially re­verse much of this dam­age. For ex­am­ple, lim­it­ing in­va­sive species – such as cane toads in Aus­tralia, mos­qui­toes in Hawaii, or rats and mice al­most ev­ery­where – could help to re­store dam­aged biomes. And elim­i­nat­ing pests’ at­trac­tion to our crops, with­out di­min­ish­ing their ca­pac­ity to ful­fill their other eco­log­i­cal roles, would re­move the need for toxic pes­ti­cides.

As we at­tempt to re­al­ize th­ese tremen­dous po­ten­tial ben­e­fits, how­ever, we must bear in mind that the ef­fects of gene drive in­ter­ven­tions will be shared by en­tire com­mu­ni­ties. Given the vast com­plex­ity of ecosys­tems, care­ful re­search will be needed to as­sess the con­se­quences of each in­ter­ven­tion be­fore pro­ceed­ing.

CRISPR gene drives also high­light a prob­lem that goes be­yond ecol­ogy: Ex­ist­ing sys­tems for de­vel­op­ing and eval­u­at­ing new tech­nolo­gies are woe­fully in­ad­e­quate for pow­er­ful new tools with broad im­pacts. It should be self-ev­i­dent that tech­nolo­gies like gene drives, which don’t re­quire wide­spread adop­tion to have a wide­spread ef­fect, should never be re­leased with­out in­formed com­mu­nity con­sent. Yet his­tory shows the op­po­site pat­tern, with de­ci­sion-mak­ing sel­dom fac­tor­ing in en­vi­ron­men­tal con­se­quences or cit­i­zens’ opin­ions.

Nowa­days, there are few op­por­tu­ni­ties for pub­lic in­put un­til af­ter prod­ucts are de­vel­oped, when it is typ­i­cally too late to make changes. By ig­nor­ing po­ten­tially help­ful con­tri­bu­tions from an in­creas­ingly knowl­edge­able pub­lic, closed-door tech­no­log­i­cal de­vel­op­ment has pre­cluded bal­anced as­sess­ments and cre­ated ac­ri­mony – a dan­ger­ously ir­re­spon­si­ble and waste­ful out­come for both sci­ence and so­ci­ety.

CRISPR gene drives of­fer an op­por­tu­nity to chart a new course. For starters, pub­lic no­ti­fi­ca­tion and broadly in­clu­sive dis­cus­sions should al­ways pre­cede and in­form de­vel­op­ment of gene drive in­ter­ven­tions in the lab. A clear de­scrip­tion of the po­ten­tial im­pact of an ex­per­i­ment – as my col­leagues and I have pro­vided for the tech­nol­ogy as a whole – must be fol­lowed by trans­parency through­out the de­vel­op­ment process. This com­mu­nity-guided ap­proach to re­search pro­vides op­por­tu­ni­ties to iden­tify and ad­dress po­ten­tial prob­lems and con­cerns dur­ing de­vel­op­ment. If a per­ceived prob­lem can­not be ad­e­quately ad­dressed, re­searchers should be pre­pared to ter­mi­nate the pro­ject.

An­other fea­ture of a re­spon­si­ble ap­proach would be a com­mit­ment by sci­en­tists to eval­u­ate each pro­posed gene drive in­ter­ven­tion – say, im­mu­nis­ing mice so that they can­not trans­mit Lyme dis­ease to ticks – in­di­vid­u­ally, rather than mak­ing a blan­ket de­ci­sion on the tech­nol­ogy as a whole. Af­ter all, the ben­e­fits and risks of each in­ter­ven­tion would be en­tirely dif­fer­ent.

A fi­nal safe­guard against the ir­re­spon­si­ble de­vel­op­ment of gene drive tech­nol­ogy is to en­sure that early in­ter­ven­tions are de­vel­oped ex­clu­sively by gov­ern­ments and non­profit or­gan­i­sa­tions. Given the po­ten­tial of fi­nan­cial in­cen­tives to skew the de­sign and re­sults of safety tests, keep­ing the profit mo­tive out of the de­vel­op­ment and de­ci­sion­mak­ing pro­cesses will en­cour­age bal­anced as­sess­ments.

The bot­tom line is that ex­ist­ing mod­els for tech­no­log­i­cal de­vel­op­ment are in­ad­e­quate for tech­nolo­gies with broadly shared ef­fects. Only with early dis­cus­sion, trans­par­ent re­search, care­ful safe­guards, and com­mu­nity guid­ance can we build a re­spon­sive model of sci­en­tific de­vel­op­ment well suited to eco­log­i­cal tech­nolo­gies. Given the life-sav­ing (and en­vi­ron­ment-sav­ing) po­ten­tial of CRISPR gene drive in­ter­ven­tions, let us de­ter­mine how to de­velop them – and when to de­cline to do so – to­gether.

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