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The Li hbea Domain
Jaime Gómez-Má quez
The ee o li e is he e olu iona y me apho o he pas and p esen
connec ions o all cellula o ganisms. Today, o speak o biodi e si y is no
only o speak o a chaea, bac e ia, and euka yo es, bu hey should also
conside he “new biodi e si y” ha includes i uses and syn he ic
o ganisms, which ep esen he new o ms o li e c ea ed in labo a o ies.
The e is e en a hi d g oup o a ificial en i ies ha , al hough no li ing
sys ems, p e end o imi a e he li ing. To emb ace and o ganize all his new
biodi e si y, I p opose he c ea ion o a new domain, wi h he name Li hbea
( om li e-on- he-bo de en i es) The c i e ia o inclusion as membe s o
Li hbea a e: i) he acellula na u e o he li ing sys em, ii) i s o igin in
labo a o y manipula ion, iii) showing new biological ai s, i ) he p esence o
exogenous gene ic elemen s, ) a ificial o ino ganic na u e. Wi hin Li hbea
he e a e wo subdomains: Vi wo ld ( om i us wo ld) which includes all
i uses, ega ded as li eless li ing sys ems, and classified acco ding o he
In e na ional Commi ee on Taxonomy o Vi uses (ICTV), and ii) Humade
( om human-made) which includes all syn he ic o ganisms and a ificial
en i ies. The ela ionships o Li hbea membe s o he h ee classical woesian
domains and hei implica ions a e b iefly discussed.
1. The Concep ual F amewo k
Unde s anding wha li e is and being able o disc imina e be-
ween wha is a li ing sys em and wha is no is o g ea concep-
ual impo ance o biology. Cla i ying hese concep s has impli-
ca ions o esea ch on he o igin o li e, he sea ch o ex a e -
es ial li e, he esolu ion o he dilemma o whe he i uses a e
ine en i ies o li ing sys ems, and o es ablishing whe he syn-
he ic o ganisms o a ificial li e o ms (he ea e A-li e) should
be conside ed li ing beings o no . Wi hou being clea abou
his, we would ne e be able o desc ibe in an in eg a ed way all
he biodi e si y (na u al o no ) ha inhabi s ou labo a o ies and
ecosys ems. The e o e, we need a concep ual amewo k ha al-
lows us, in he fi s place, o es ablish whe he i uses and all
J. Gómez-Má quez
Depa men o Biochemis y and Molecula Biology
Uni e si y o San iago de Compos ela
San iago de Compos ela, Galicia 15782, Spain
E-mail: [email p o ec ed]
The ORCID iden ifica ion numbe (s) o he au ho (s) o his a icle
can be ound unde h ps://doi.o g/10.1002/adbi.202300679
© 2024 The Au ho s. Ad anced Biology published by Wiley-VCH GmbH.
This is an open access a icle unde he e ms o he C ea i e Commons
A ibu ion License, which pe mi s use, dis ibu ion and ep oduc ion in
any medium, p o ided he o iginal wo k is p ope ly ci ed.
DOI: 10.1002/adbi.202300679
hese syn he ic o ganisms and li e o m
A ha make up he new biodi e si y a e
li ing beings o no , o be able o classi y
hem in a cohe en way. Un o una ely,
he scien ific communi y has no ye es-
ablished a uni e sally accep ed doc ine
on he defini ion o li e and li ing being,
hence my e e ence in his s udy is my
p oposal on bo h concep s.[1]
My defini ion o li e a ises om he
analysis o he se en ai s common
o all li ing sys ems: i) o ganic na u e
( he biochemis y o li e is based on
he chemis y o ca bon), ii) en opy-
p oducing (li ing beings a e open he -
modynamic sys ems ha p ese e hei
in e nal o de by expo ing en opy o
he ou side), iii) sel -o ganizing (sys-
ems a om he modynamic equilib-
ium o dissipa i e s uc u es can spon-
aneously sel -o ganize), i ) ewo kable
p e-p og am (all li ing sys ems con-
ain a mu able molecula p og am w i -
en in hei genome), ) capaci y o
in e ac and adap (any li ing sys em
de elops i s i al unc ions h ough mul iple in e ac ions and is
capable o adap ing o new ci cums ances), i) ep oduc ion and
ii) e olu ion ( ep oduc ion allows he pe pe ua ion o species
and makes he e olu iona y p ocess possible).
F om he analysis o hese ai s, I define li e as an in e ac i e
p ocess occu ing in en opy-p oducing, adap i e, and in o ma-
i e o ganic sys ems. No e ha his defini ion o li e does no in-
clude ep oduc ion and e olu ion because bo h ai s a e no nec-
essa y o li e; hey a e op ional o acul a i e ai s because no
all o ganisms ep oduce and/o e ol e (e.g., a s e ile animal such
as a mule canno ep oduce bu is ne e heless a li ing being).
Acco ding o his defini ion o li e, a li ing being is an en opy-
p oducing, adap i e, and in o ma i e o ganic sys em, i.e., he li -
ing sys em is he “con aine ” whe e he i al p ocess akes place.
No e he impo ance o he sys em-p ocess duali y, which means
ha wi hou he li ing being ( he sys em) he e is no li e, and
wi hou li e ( he p ocess) he li ing being ceases o be o de ed
and decays.[1]
Wi h his defini ion, i is easy o see why a olcanic ock, a
qua z c ys al, a complex algo i hm, o a me allic obo a e no
s uc u es ha we can iden i y and classi y as li ing sys ems. Fo
example, a qua z c ys al, al hough i is a highly o de ed s uc-
u e like any li ing being, is no a li ing sys em because i is
nei he an o ganic sys em, no does i ha e gene ic in o ma-
ion, no does i can adap o e ol e (e olu ion is a consequence
o he adap i e p ocess) h ough some hing like mu a ion and
ep oduc ion.
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2. Vi uses as Li eless Li ing Sys ems
The biological significance o i uses is unques ionable, and hey
should no be igno ed i we a e o unde s and he p ocesses o
ho izon al gene ansmission, he cause o many diseases, he
e olu ion o species, he dynamics o ecosys ems, o he bio-
geochemical cycles.[2–6]Despi e his, i uses ha e been sys em-
a ically excluded as componen s o biodi e si y because o hei
acellula na u e and because hey we e no conside ed li ing
beings.[7]
A e i uses li ing sys ems? This ques ion aises one o he
mos p ominen con o e sies in he field o biology. Vi uses a e
somewhe e be ween li ing and ine : when hey a e ou side he
cell, hey a e passi e s uc u es wai ing o he momen o in ec
hei biological hos , bu when hey find i , i uses de elop hei
en i e i al s a egy o pe pe ua e hemsel es. Ou side he cell,
i uses only ha e he po en ial o in ec cells, hey a e jus highly
o ganized and in o ma i e o ganic sys ems ha show no signs o
li e, hey a e li eless li ing sys ems. On he con a y, when a i us
in ec s a cell, i mani es s all he cha ac e is ics o a li ing sys em
(en opy p oduc ion, exp ession o i s gene ic in o ma ion, sel -
o ganiza ion, capaci y o in e ac ion and adap a ion, ep oduc-
ion, and e olu ion) and, as i mee s all he equi emen s o be
ali e, i should be conside ed a li ing sys em.[1]
In sho , i uses a e obliga e in acellula pa asi es ha do no
need o be a cell bu , like any pa asi e, use hei hos o hei
own benefi . Vi uses pu sue he same goals as all li ing cellu-
la beings: o su i e and ep oduce o emain in he hos cell.
The i al duali y be ween he ine o ganic sys em (ou side he
cell) and he li ing sys em (du ing he in ec ion) is wha makes
i uses o be conside ed as li eless li ing beings and, he e o e,
as componen s o he biodi e si y ha exis s on ou plane .
3. Syn he ic O ganisms and A-Li e Fo ms
In he mids o he biological e olu ion b ough abou by he
g ea concep ual and echnological ad ances in many a eas e-
la ed o he li e sciences, syn he ic o ganisms a e playing a ma-
jo ole in he de elopmen o ou socie y. They a e li ing en-
i ies ha a e no he esul o a na u al e olu iona y p ocess
bu ha e been manu ac u ed h ough di ec cellula o gene ic
manipula ion.[8]Syn he ic biology in ol es edesigning o gan-
isms o use ul pu poses by enginee ing hem o ha e new abili-
ies, consequen ly, syn he ic o ganisms, unde s ood as biological
en i ies cons uc ed in he labo a o y om na u al biological sys-
ems, a e li ing sys ems because hey mee all he equi emen s
necessa y o he li e p ocess.[1]Syn he ic biology is al eady ans-
o ming he way we g ow ood, p oduce subs ances o heal h in-
e es , ca y ou ce ain indus ial p ocesses, e c., and i s impo -
ance will inc ease o e ime.[9,10]
In a b oad sense, A-li e could be unde s ood as he syn he-
sis and simula ion o li ing sys ems, being mo e closely ela ed
o a ificial in elligence (he ea e AI) and he design o en i ies
ha aim o mimic he li ing,[11,12]as compa ed o syn he ic bi-
ology ha aims o build new li ing sys ems ha a e based on
o ganic ma e , i.e., ca bon biochemis y. Th ee ypes o A-li e
a e commonly men ioned in he scien ific li e a u e: i) so A-li e
(so om so wa e), which deals wi h ma hema ical and com-
pu a ional models; ii) ha d A-li e (ha d om ha dwa e), which
e e s p ima ily o mechanical obo s; iii) we A-li e, which in-
cludes syn he ic o ganisms based on ca bon chemis y.[13]So
and ha d A-li e canno be conside ed as li ing en i ies because
nei he compu e p og ams no obo s o obo -like de ices a e
cons uc ed and unc ion acco ding o he biochemis y o li e,
hey do no mee he equi emen s o be conside ed as a li ing
sys em.[1,14]Howe e , we A-li e is e y diffe en om so and
ha d A-li e, and since i uses o ganic ma e o c ea e new biolog-
ical en i ies i alls wi hin he field o syn he ic biology[8,15];Ido
no conside we A-li e o ms as a ificial en i ies bu ue li ing
sys ems because hey mee all he cha ac e is ics o be ali e.
In b ie , we could define syn he ic o ganisms as au hen ic li -
ing sys ems ha , no being he esul o a na u al e olu iona y
p ocess, ha e all he necessa y cha ac e is ics o de elop he i al
p ocess, while A-li e (so and ha d) a e non-li ing en i ies ha
imi a e li ing ones.
4. B ie Conside a ion o A ificial Selec ion
T adi ionally, a ificial selec ion echniques ha e been used o di-
ec he e olu ion o species o ag icul u al and li es ock o com-
panion animal in e es .[16]Thus, he esea che selec ed he p e-
e ed ai and hen b eed he o ganism o p oduce offsp ing
wi h he desi ed pheno ype. A ificial selec ion is synonymous
wi h human-di ec ed e olu ion, and, like na u al selec ion, i
wo ks by selec ing geno ypes and pheno ypes, excep ha in he
la e i is na u e ha makes he decisions abou which gene ic
changes should emain in he species. I conside ha he o gan-
isms ob ained by a ificial selec ion canno be qualified s ic ly
as syn he ic o ganisms because nei he he sys em used o ob-
ain hem (selec i e b eeding ha al e s gene equencies) no he
modifica ions in he genome we e ob ained by di ec gene ic ma-
nipula ion al e ing he gene con en , he gene ic code, o wha -
e e i may be.
5. The T ee o Li e and he New Biodi e si y
When we alk abou biodi e si y and he e olu ion o species,
we always u n o he “ ee o li e”, a b illian idea echoed by
Da win[17]in his seminal book on he o igin o species by na -
u al selec ion when he w o e: “The affini ies o all he beings
o he same class ha e some imes been ep esen ed by a g ea
ee. I hink his simile la gely speaks he u h”. In his line,
in he la e 20 h cen u y, i was p oposed a new concep ion o
he “ ee o li e” ha g ouped cellula o ganisms in o h ee do-
mains: A chaea, Bac e ia, and Euka ya, as he highes ank o
classifica ion.[18]La e on, he disco e y o a my iad o di e se
a chaeal lineages changed ou unde s anding o he e olu ion-
a y ela ionships among he h ee domains o li e and he o igin
o euka yo es.[19]A he p esen ime, wi h he genome e olu-
ion unde way, he classifica ion o biodi e si y is inc easingly
efined, al hough a consensus ha sa isfies he en i e scien ific
communi y has no ye been eached.[20,21]
In he 21s cen u y, do he cu en ees o li e in hei many
a ian s ep esen all he biodi e si y on ou plane ? And he an-
swe I unde s and should be nega i e because i uses a e no
he e, and nei he a e syn he ic o ganisms (I do no mean o
say ha hese ees a e w ong bu ha hey do no include all
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GEO
WLO SCS
Ha d
A-Li e
So
A-Li e
GMO
SGO
CAO
We A-Li e
Va idna i ia
Monodna i ia
Duplodna i ia
Adna i ia
Ribozy i ia
Ribo i ia
ILS/
ACC
Syn he ic
O ganisms
Li eless Li ing Sys ems
(ICTV Taxonomy) Syn he ic Li ing Sys ems Non-Li ing
Sys ems
A-Li e
Fo ms
SRO
HUMADEVIRWORLD
SCOSVS
LSC
ASC
UGC
Wei d
mix
GED
TGO
GMV
SGV
Va idna i ia
Monodna i ia
Duplodna i ia
Adna i ia
Ribozy i ia
Ribo i ia
Li eless Li ing Sys ems
(ICTV Taxonomy)T
T
VIRWORLD
GEO
WLO SCS
GMO
SGO
CAO
We A-Li e
ACC
Syn he ic Syn he ic
Syn he ic
O
O
ganisms
ganisms
Syn he ic Li ing Sys ems
SRO
HUMADE
SCOSVS
LSC
ASC
UGC
Wei d
mix
GED
TGO
GMV
SGV
e A-Li e
ILS/
ACC
HUMADE
The Li hbea Domain
Ha d
A-Li e
So
A-Li e
e A-Li e
ILS/
ACC
Non-Li ing
Sys ems
A-Li e
Fo ms
HUMADE
e A-Li e
ILS/
ACC
HUMADE
e A-Li e
ILS/
ACC
HUMADE
Figu e 1. The Li hbea domain. This domain is di ided in o wo e olu iona ily un ela ed subdomains: Vi wo ld, which includes all ealms o i uses
ollowing ICTV ules, and Humade ha comp ises all human-made en i ies. Syn he ic o ganisms a e non-na u al li ing sys ems (excep o ILS), and
A-li e o ms ha a e non-li ing sys ems ( he double-a owed do ed line indica es ha we -li e should be included wi hin he A-li e o ms and syn he ic
o ganisms). SVS, syn he ic i al sys ems; GMV, gene ically modified i uses; SGV, syn he ic genome i uses; SCO, syn he ic cellula o ganisms; WLO,
wei d li ing o ganisms ( he exp ession “wei d mix” e e s o all hese s ange o ganisms such as he xenobo s o he sys em known as b ainowa e);
GEO, gene ically enginee ed o ganisms; SGO, syn he ic genome o ganisms; GMO, gene ically modified o ganisms; TGO, ansgenic o ganisms; GED,
gene-edi ed o ganisms; CAO, codon-al e ed o ganisms; ASC, al e ed s anda d code; UGC, unna u al gene ic code; SRO, syn he ic eplicon o ganisms;
SCS, syn he ically cellula sys ems; LSC, li ing syn he ic cells; ILS/ACC, incomple e li ing sys ems/a ificially c ea ed cells.
biodi e si y). Unlike i uses, he appa en exclusion o syn he ic
o ganisms om he ee o li e is due o he ac ha hese c ea-
u es a e no he esul o he na u al e olu iona y p ocess, al-
hough some o hem could be included wi hin A chaea, Bac e ia,
o Euka ya because hey did no lose hei essence as a species,
i.e., a ansgenic mouse is s ill a mouse al hough i is no longe
he exclusi e ui o he e olu iona y p ocess.[14]The e a e o he
syn he ic o ganisms ha a e e y diffe en om any known cellu-
la o m and ha could no be included o esemble any o ganism
belonging o he Woesian domains.
6. The Li hbea Domain
The Li hbea domain, an ac onym o “LIFE-on-THE-Bo de En i-
ies”, was bo n om he idea o g ouping and classi ying all hose
biological ( i uses and syn he ic o ganisms) and biological-like
(A-li e) en i ies ha we e no included in he ee o li e (i should
be no ed ha lineage and phylogeny ha e no been de e mining
ac o s o he classifica ion sys em p esen ed he e). The A-li e
o ms a e included because al hough we canno conside hem
as ue li ing sys ems, hey esemble hem mo e and mo e and
help us o unde s and he phenomenon o li e.[14]Figu e 1shows
he complexi y o he Li hbea domain.
The c i e ia o en e ing Li hbea a e: i) he acellula na u e
o he li ing sys em (e.g., i uses), ii) he non-na u al o igin o
he li ing sys em (e.g., ansgenic o ganisms), iii) he p esence
o no el biological ai s (e.g., xenobo s), i ) he p esence o ex-
ogenous gene ic elemen s (e.g., plasmids), and ) he a ificial o
ino ganic na u e o en i ies ha mimic he li e p ocess o he li -
ing sys em (e.g., A-li e o ms).
In Li hbea he e a e wo subdomains: Humade (a e m de i ed
om he con ac ion o he exp ession Human-made) which in-
cludes all syn he ic o ganisms and A-li e o ms, and Vi wo ld (a
e m de i ed om he con ac ion o he exp ession Vi al wo ld),
which includes all i uses p esen in na u e (ob iously i uses
could also be c ea ed in he labo a o y and hus o m pa o syn-
he ic en i ies). Unlike he ee o li e ha shows us he exis ence
o common ances o s, he en i ies belonging o Li hbea do no
ha e a common ances o and, consequen ly, he cons uc ion o
he ee o li e o he Li hbea domain is no based on phylogeny
and ances y, bu on he c i e ia men ioned abo e. On he o he
hand, i should be no ed ha he en i ies belonging o Humade
and Vi wo ld a e no isola ed en i ies bu can in e ac wi h each
o he and wi h p oka yo ic and euka yo ic o ganisms. Fu he -
mo e, ce ain syn he ic o ganisms included wi hin Li hbea, such
as ansgenic o ganisms, ha e no los hei species iden i y and
he e o e migh also o m pa o he Woesian domains e en i
hei o igin is no longe comple ely na u al.
7. The Vi al Subdomain (Vi wo ld)
The e a e se e al ways o classi y i uses conside ing aspec s
such as capsid s uc u e, nucleic acid ype, physical p ope ies,
hos species, o he disease caused by hei in ec ion.[22]In
his espec , i has been ecen ly p oposed ou p inciples o
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ecommenda ions o guide he cons uc ion o a cohe en and
comp ehensi e i us axonomy.[23]
Wi hin he Li hbea domain, he i al subdomain includes all-
na u al i uses classified acco ding o he In e na ional Commi -
ee on Taxonomy o Vi uses (ICTV) axonomy (Figu e 1shows
only he six ealms). The ICTV is he official body ha classifies
i uses and by con as o he axonomy o cellula o ganisms, he
axonomic amewo k o i uses mus adap o he cu en iew
ha i uses ha e mul iple o igins (polyphyly) and ha hei di e -
si y canno be ep esen ed in a single ee ha encompasses he
en i e i osphe e.[24,25]So a he e a e six ealms wi hin he ICTV
axonomy, each o which is in e ed o ep esen a unique mono-
phyle ic e olu iona y o igin o i s componen i uses, al hough
ecen e idence sugges s ha he numbe o independen and
ancien e olu iona y o igins o i uses may be e en g ea e .[25,26]
T ying o figu e ou he e olu iona y his o y o i uses is asci-
na ing. Vi uses may ha e a isen om mobile gene ic elemen s,
may ha e p eceded cellula li e, may ha e o igina ed om ee-
li ing o ms ha became obliga e in acellula pa asi es, o may
ha e a isen by a ye unknown mechanism.[27,28]Biologis s ha e
deba ed how o classi y hese li eless li ing hings and how o e-
la e hem o he ee o li e. The main p oblem is ha we do no
know o su e wha has been o wha hei o igins ha e been,
bu wha e e i is, i uses and hei hos s ha e been ecologically
and e olu iona ily in e wined.[4,29]Be ha as i may, a uni e sal
axonomy o i uses is essen ial o a comp ehensi e iew o he
i osphe e and hei e olu iona y ela ionships.
8. The Human-Made Subdomain (Humade)
The Humade subdomain comp ises all syn he ic o ganisms and
A-li e o ms and is di ided in o wo majo g oups: i) Syn he ic o -
ganisms (non-na u al o ganic li ing sys ems) and ii) A-li e o ms
(non-li ing sys ems ha mimic li e). As I men ioned ea lie , we
A-li e en i ies would be included in he g oup o syn he ic o gan-
isms al hough some esea che s include hem as a ype o A-li e
( his duali y is shown in Figu e 1).
9. Syn he ic O ganisms
Syn he ic biology expands he biodi e si y o he plane by con-
s uc ing new o ganisms wi h s uc u al and/o unc ional el-
emen s ha a e diffe en om na u al ones.[8,15]I s de elop-
men has gone hand in hand wi h ad ances in molecula biology,
bio echnology, and, mo e ecen ly, AI, and syn he ic o ganisms
will inc easingly ha e a wide ange o applica ions in a ious sec-
o s, such as medicine, ag icul u e, ene gy, manu ac u ing, and
ood. The u u e will b ing us hi he o unimaginable c ea u es
ha will be inc easingly p esen in ou socie ies and ecosys ems.
Wi hin syn he ic o ganisms he e a e wo ca ego ies: i) Syn-
he ic Vi al Sys ems (SVS), and ii) Syn he ic Cellula O ganisms
(SCO). The c i e ion o es ablishing hese wo ca ego ies is he
acellula o cellula na u e o biological en i ies. SVS includes all
i uses employed in gene ic enginee ing- ela ed echniques and
i uses whose genome has been syn hesized in he labo a o y.
SCO a e classified acco ding o he ype o gene ic manipula ion
hey ha e unde gone and he way hey ha e been c ea ed in he
labo a o y.
SVS is di ided in o wo diffe en classes: i) Gene ically Mod-
ified Vi uses (GMV), and ii) Syn he ic Genome Vi uses (SGV).
SCO is di ided in o h ee diffe en classes: i) Gene ically Engi-
nee ed O ganisms (GEO), ii) Wei d Li ing O ganisms (WLO),
and iii) Syn he ic Cellula Sys ems (SCS).
10. The SVS (Syn he ic Vi al Sys ems)
SVS comp ises all i uses whose genome has been modified o
cloning, medical o bio echnological applica ions ( ecombinan
i uses o GMV), and i uses whose genome has been wholly o
pa ially syn hesized in he labo a o y (SGV).
GMVs a e i uses ha ha e been gene ically modified by in-
se ion, dele ion, o mu a ion in he i al genome wi hou los-
ing hei abili y o in ec . GMVs ha e been used o mul iple pu -
poses ela ed o cloning, DNA sequencing, o basic biological e-
sea ch, as well as o medical, ag icul u al, pha maceu ical, and
bio echnological pu poses.[30,31]In medicine, GMVs can be used
o a ge and des oy cance cells, ea a ious gene ic diseases as
gene and cell he apy ools, o se e as accines o accine deli -
e y agen s.[32]Fo example, diffe en i al ec o s ha e been used
in p eclinical and clinical ials as accines agains se ious dis-
eases caused by in ec ious agen s such as HIV, and Plasmodium
sp.(Mala ia), Ebola and SARS-CoV-2.[33]
The combina ion o echniques in he field o syn he ic bi-
ology and compu a ional biology has led o he p oduc ion o
i uses whose genome is syn he ic, manu ac u ed in whole o
in pa in he labo a o y. The fi s i us assembled om syn-
he ic oligonucleo ides was a polio i us.[34]This miles one in syn-
he ic i ology was ollowed by he gene a ion o he fi s syn-
he ic genome co esponding o bac e iophage phiX174.[35]Sub-
sequen ly, he cons uc ion o an in ec ious ho sepox i us in
2018 om syn hesized DNA aised conside able doub s and con-
ce ns abou he possibili y o c ea ing human pa hogenic i uses
in he labo a o y.[36]Syn he ic i ology has come a long way, and
i s u u e looks e y p omising, wi h nume ous posi i e applica-
ions anging om medicine o ag icul u e, al hough no wi h-
ou isks.[37,38]We now ha e he echnological powe o esu ec
i uses o c ea e new i uses in he labo a o y o mul iple pu -
poses. In his sense, scien is s, legisla o s, and socie y in gene al
should ac esponsibly by making a easonable balance be ween
p og ess and he dange s associa ed wi h his powe ul echnol-
ogy.
11. SCO (Syn he ic Cellula O ganisms)
11.1. The GEO (Gene ically Enginee ed O ganisms)
Redesigning o ganisms o p oduce a ce ain subs ance like ans-
genic ice wi h be a-ca o ene o acqui e a new capaci y like bac-
e ia used o bio emedia ion, a e wo examples o he ini ial
goals in syn he ic biology. Since hen, scien ific p og ess is lead-
ing us o ad ances in genome manipula ion ha we e un hink-
able no long ago. GEO includes o ganisms whose gene ic ma e-
ial ( he genome o he gene ic code) has been modified o gi e
hem new p ope ies, o ganisms whose genome is ully syn he ic
o semi-syn he ic, and o ganisms ha con ain ex ach omoso-
mal elemen s. The e a e ou g oups o GEO: Gene ically Mod-
ified O ganisms (GMO), Syn he ic Genome O ganisms (SGO),
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Codon-Al e ed O ganisms (CAO), and Syn he ic Replicon O gan-
isms (SRO).
11.1.1. The GMO (Gene ically Modified O ganisms)
A GMO is a gene ically modified o ganism whose genomic modi-
fica ions a e no he esul o selec i e ma ing (a ificial selec ion)
o na u al ecombina ion, bu he esul o DNA manipula ion
in he labo a o y. DNA sequences can be in oduced, amplified,
o dele ed wi hin a species, be ween species, o e en be ween
kingdoms. The e a e wo ypes o GMO: ansgenic (TGO) and
gene/genome-edi ed (GED) o ganisms.
A TGO is a li ing sys em whose gene ic composi ion has been
modified by in oducing a o eign gene by means o bio echno-
logical echniques. TGOs a e used o basic biological esea ch
as well as o applica ions ela ed o ood supply, human heal h
like he p oduc ion o subs ances o he apeu ic in e es , and he
mi iga ion o en i onmen al pollu ion. DNA can be ans e ed
wi hin indi iduals o he same species like a ansgenic mouse ex-
p essing lac ase in he mamma y gland o p oduce low–lac ose
milk in i o,[39]be ween diffe en species like he in oduc ion
o abbi DNA agmen s con aining he be a-globin gene in o
mouse ge m-line cells[40]o e en be ween kingdoms like he ex-
p ession o fi efly luci e ase gene in ansgenic obacco lea es.[41]
In he GED o ganisms, he al e a ion o he genome is
pe o med using nucleases ha ha e been enginee ed o a -
ge a specific DNA sequence, whe e hey in oduce cu s en-
abling he emo al o exis ing DNA and he inse ion o e-
placemen DNA.[42,43]Gene edi ing in ol es he inse ion (gene
knock-in), silencing (gene knock-ou o loss-o - unc ion), dele-
ion, o eplacemen o DNA o ob ain a new unc ion o
pheno ype.[44]O pa icula in e es is he clus e ed egula ly
in e spaced sho palind omic epea s/CRISPR-associa ed p o-
ein 9 (CRISPR/Cas9) echnology, whose applica ions ha e p o-
oundly changed biological esea ch.[45]CRISPR-Cas genome
edi ing sys ems ha e ans o med ou abili y o manipula e, de-
ec , and isualize specific DNA and RNA sequences in li ing
cells. The ease, accu acy, affo dabili y, and o his sys em o-
bus ness o his echnology ha e e olu ionized genome edi ing
o esea ch anging om undamen al science o ansla ional
medicine.[46,47]Fo example, he high efficiency and accu acy o
he CRISPR/Cas9 echnique allow us o explo e he unc ions
o cance - ela ed genes, g ea ly inc easing ou unde s anding o
cance genomics.[48]Al hough his echnique has appa en ad-
an ages o gene he apy, CRISPR/Cas9 b ings i s own se o
limi a ions which mus be add essed o sa e and efficien clinical
ansla ion.[49]Ano he example o he powe o his echnology
is he edi ion o genes in ol ed in me abolic pa hways o c ea e
o ganisms ha p oduce aluable compounds such as bio uels,
d ugs, and indus ial chemicals.[50]The inco ec use o CRISPR-
Cas echnology could pose a isk and dange ; he deba e abou he
implica ions o his echnology bo h in he scien ific communi y
and in socie y is impo an .
In addi ion o o he issues un ela ed o biology, GMOs could
ha e e y se ious impac s on biodi e si y i hey in e ac wi h na -
u al species. In his ega d, he p oduc ion o ansgenic animals
and c ops has aised conce ns abou hei po en ial ecological im-
pac , especially i hese o ganisms escape o a e eleased in o he
wild and may in e b eed wi h wild flo a and auna. Ob iously,
he same o e en g ea e conce ns a ise when we hink o gene -
ically modified mic oo ganisms because hei abili y o mu a e
and ep oduce is much g ea e . Th ee diffe en examples o hese
GMO-na u e in e ac ions and he isks associa ed wi h hem a e
as ollows:
i. In e specific hyb idiza ion be ween A lan ic salmon (Salmo
sala ) and b own ou (Salmo u a) has been demons a ed
h ough expe imen al c osses using he g ow h ho mone
ansgene.[51,52]In his pa icula case, his in e specific hy-
b idiza ion (which could also occu among many o he eu-
ka yo ic and p oka yo ic species) makes i necessa y o assess
he ecological and e olu iona y consequences o he p esence
o hese g ow h-accele a ed gene ically enginee ed fishes in
na u al ecosys ems.
ii. The in og ession o ansgenes om gene ically modified
c ops o hei wild ela i es has been widely epo ed.[53]Mo e
ecen ly, i has been shown he ecological and e olu iona y
consequences o ansgene in og ession in a Mexican wild
co on (Gossypium hi su um)popula ion.
[54]In gene al e ms,
we could say ha he biological consequences o he p es-
ence o one o mo e ansgenes in a wild species will depend
la gely on he ype o ansgene, i s inse ion si e, he plan
densi y, and ecological ac o s.
iii. The p esence o ansgenic mic obes ou side he labo a o y
could lead o hei uncon olled sp ead, affec ing ecological
p ocesses h ough in e ac ion wi h na i e popula ions and
ood chains. In addi ion, he e would be he isk o ans e o
ansgenic DNA by ho izon al gene ans e ha could gi e
ise o new pa hogens. All his makes i impo an o ake
all he necessa y p ecau ions o a oid unp edic able nega i e
consequences ha a e e y difficul o e e se.[55]
11.1.2. The SGO (Syn he ic Genome O ganisms)
Syn he ic genomics is a nascen field o syn he ic biology ha
in ol es wo basic ope a ions: he syn hesis o comple e genomes
o ch omosomes and he u iliza ion o hese syn he ic nucleic
acids o make i uses o li ing cells. In his con ex , SGOs a e
hose syn he ic o ganisms whose genome has been en i ely o
pa ially syn hesized in he labo a o y.[56,57]In he nea u u e, he
c ea ion o new SGOs will ha e a s ong impac on many a eas
o ou socie y ela ed o medicine o bio echnology such as, o
example, he de elopmen o he nex gene a ion o accines o a
new indus ial e olu ion o p oduce ood and chemicals.
The fi s syn he ic bac e ial genome was comple ed in 2008
wi h he syn hesis o he genome o Mycoplasma geni alium
(named as M. geni alium JCVI-1.0), a bac e ium ha can cause
u ina y and geni al ac in ec ions in humans.[58]This achie e-
men ma ked an impo an miles one in syn he ic biology be-
cause i was he fi s ime a comple e genome was syn hesized
om sc a ch in a labo a o y. The ea e , he same eam con-
s uc ed Mycoplasma mycoides (M. mycoides) JCVI-syn1.0, he
fi s li ing cell wi h a ully a ificial genome, by fi s syn hesiz-
ing he bac e ial ch omosome sequence and hen ans e ing i
in o a Mycoplasma cap icolum (M. cap icolum) ecipien cell o
c ea e new M. mycoides cells con olled solely by he syn he ic
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ch omosome.[59]In 2016, he gene ic in o ma ion o JCVI-syn1.0
was educed o p oduce JCVI-syn3.0, which ha bo s he smalles
genome – 531 kb and 438 genes – o any ee-li ing p oka yo e.[60]
La e on, i was c ea ed JCVI-syn3A o be e g ow h, demon-
s a ing he polygenic na u e o cell di ision and mo phology in
a minimal cell.[61]
Genome minimiza ion and e- unc ionaliza ion a e e y a -
ac i e esea ch opics because minimal genomes ( he smalles
possible numbe o genes equi ed o suppo a li ing cell un-
de a defined se o condi ions) may help o find an answe o
age-old ques ions like Wha is li e? and imp o e he applica ions
o syn he ic biology.[62]In his ega d, he educed genome o
he syn he ic bac e ium JVC-syn3A was modified o include he
Spi oplasma genes in ol ed in mo ili y o c ea e he smalles -e e
mo ing cell.[63]Mo eo e , na u al selec ion can apidly inc ease
he fi ness o a syn he ically cons uc ed minimal cell ha has
been s ipped o all bu i s essen ial genes, demons a ing he ca-
paci y o a minimal cell o su i e and e ol e (Mo ge –Reische
e al. 2023).[64]
In he euka yo ic wo ld, a s ain o he yeas Sacha omyces ce e-
isiae (S. ce e isiae) whose genome is mo e han 50% composed
o syn he ic DNA has been p oduced by combining se en syn-
he ic ch omosomes in o a single yeas cell, esul ing in a s ain
wi h mo e han 50% syn he ic DNA ha su i es and eplica es
simila ly o wild yeas s ains.[65]This disco e y is a miles one
in SGO esea ch because, un il now, scien is s ha e gene a ed
a ificial genomes om a ious i uses and bac e ia, bu yeas
would be he fi s euka yo ic o ganism wi h a iable genome pa -
ially gene a ed in he labo a o y.[66]Ve y ecen ly, he in i o as-
sembly o ch omosomal agmen s in he moss Physcomi ium
pa ens has been published.[67]The esea che s p oduced pheno-
ypically nea -wild lines o he moss in which one- hi d o he
coding egion o a ch omosomal a m is eplaced by chemically
syn hesized, edesigned agmen s. We a e only a he begin-
ning o his new genomic e olu ion and hese ad ances wi h
yeas and moss a e pa ing he way o he syn hesis o new
euka yo ic genomes and opening many windows o s udy he
unc ioning o genomes and o he c ea ion o new “ amazing”
o ganisms.
11.1.3. The CAO (Codon-Al e ed O ganisms)
The gene ic code e e s o he se o ins uc ions needed o con-
e he in o ma ion con ained in p o ein-coding genes in o p o-
eins, and i is i s uni e sali y ha allows o ganisms o exchange
gene ic in o ma ion, e en be ween e olu iona ily dis an species,
and o exp ess an euka yo ic p o ein in bac e ia. The echnolog-
ical ad ances in gene ic enginee ing no only allow us o c ea e
syn he ic genomes bu also o al e he gene ic code.[68]He e, we
define CAO en i ies as syn he ic o ganisms in which he gene ic
code has been al e ed. In his ype o li ing sys em, we a e modi y-
ing he gene ic code o change he sequence o codons, o educe
he numbe o iple s, o o in oduce new unna u al codon a i-
an s. The e is no doub ha CAO o ganisms could be e y use ul
in he p oduc ion o syn he ic p o eins, o in he design o new
subs ances.
The e a e wo main a ian s o o ganisms wi h he na u al ge-
ne ic code al e ed: i) ASC ( om Al e ed S anda d Code) ha in-
cludes hose li ing sys ems wi h a ia ions in he numbe o s an-
da d codons o eassigning he significance o he codons, and ii)
UGC ( om Unna u al Gene ic Code) ha includes hose o gan-
isms wi h non-na u al iple s and/o non-na u al amino acids.
To syn hesize p o eins, he ansla ion machine y o he cells
uses 64 iple codons o he canonical 20 amino acids; 18 o
hese amino acids a e encoded by mo e han one codon which
means ha he gene ic code is edundan . The fi s ASC o gan-
ism was a a ian o Esche ichia coli (E. coli) wi h he numbe
o codons used o encode canonical amino acids educed o 61,
by genome-wide eplacemen o a ge codons wi h defined syn-
onyms. To achie e his educ ion, 18214 codons we e ecoded o
c ea e an o ganism ha uses 59 codons o encode he 20 amino
acids and enables he dele ion o a p e iously essen ial ans-
e RNA.[69]The gene a ion o o ganisms wi h a educed ge-
ne ic code, a oiding edundancies wi hou losing in o ma ion,
has been a majo scien ific achie emen ha has shown ha
li e can ope a e wi h a educed numbe o synonymous sense
codons. A diffe en example o al e a ions o he gene ic code
was he de elopmen o E. coli cells wi h an amino acid-swapped
gene ic code ha eassigns wo o he six codons om se ine
o leucine du ing ansla ion, making he cells esis an o i-
al in ec ion.[70]This amino acid-swapped gene ic code makes
cells comple ely esis an o i al in ec ions by mis ansla ing i-
al p o eomes and p e en s leakage o syn he ic gene ic in o ma-
ion by elying on se ine codons o p oduce p o eins ha equi e
leucine. As he au ho s sugges , hese findings may p o ide he
basis o make any o ganism sa ely esis an o all na u al i uses
and p e en gene ic in o ma ion flow in o and ou o gene ically
modified o ganisms.
The UGC o ganisms a e syn he ic li ing sys ems wi h an
expanded nucleo ide alphabe by making DNA wi h unna u al
nucleo ides.[68]Expansion o he gene ic code, in which a sin-
gle amino acid is eplaced by a non-na u al amino acid, is also a
way o c ea e new p o eins o o label p o eins wi hou dis u bing
hei s uc u e and hus o be e isualize hem in li ing cells.[71]
One o he pionee ing expe imen s in his field was he use o en-
ginee ed RNAs capable o inco po a ing non-canonical amino
acids using ou -le e codons.[72,73]Subsequen ly, i was c ea ed a
semisyn he ic o ganism ha can s ably s o e gene ic in o ma ion
using a six-le e , h ee-base-pai alphabe [74]and i was demon-
s a ed o he fi s ime ha syn he ic o ganisms can use non-
na u al nucleo ides o DNA eplica ion, RNA ansc ip ion, and
p o ein ansla ion in i o.[75]Ano he majo miles one in syn-
he ic biology was he cons uc ion o “Hachimoji” DNA which
is a gene ic sys em composed o eigh le e s ha can be an-
sc ibed by a modified RNA polyme ase in he labo a o y.[76]The
applica ions o modi ying o ex ending he gene ic code a e po-
en ially eno mous, bu we should be awa e o he po en ial isks
o hese echnological ad ances.
Na u e also expe imen s wi h a ian s o he ACGT alphabe .
This is he case o he genome o ce ain bac e iophages in which
adenine (A) has been subs i u ed by 2-aminoadenine (Z). These
phages con ain DNA wi h an al e na i e gene ic alphabe (ZTGC)
ha e ades he a ack o bac e ial es ic ion enzymes allowing
he pe sis ence o hese i uses in oxic en i onmen s.[77]Gi en
ha ou knowledge o he i osphe e is a om comple e, one
wonde s how many su p ises i s s udy will b ing us in he coming
yea s, and he e will p obably be many.
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11.1.4. The SRO (Syn he ic Replicon O ganisms)
Replicons a e uni s o DNA ha can eplica e au onomously
wi hin a sui able hos . Syn he ic Replicon O ganisms (SRO)
a e o ganisms ha ha e been ans o med wi h a eplicon o
gi e hem one o mo e new unc ions. This is he case o uni-
cellula o ganisms (bac e ia and yeas s) ans o med wi h plas-
mids, a eplicon widely employed in ecombinan DNA ech-
nology o gene ic enginee ing. Plasmids a e ex a-ch omosomal
ci cula double-s anded DNA molecules ha eplica e indepen-
den ly o ch omosomal DNA. Scien is s ha e ha nessed plas-
mids as cloning ec o s o ampli y and manipula e genes and
DNA agmen s, as well as o exp ess ecombinan p o eins in
well-es ablished p oka yo ic and euka yo ic hos s, such as E. coli
o S. ce e isiae. These o ganisms ans o med wi h ecombinan
plasmids p oduce impo an chemicals such as biopolyme s o
bio uels and p o eins like insulin o g ow h ho mone o high
he apeu ic alue.[78]In addi ion, designing and cons uc ing
plasmids om smalle agmen s o o m complex unc ional
DNA molecules (such as biochemical pa hways and gene ic ci -
cui s) is an excellen syn he ic echnology o molecula biology
s udies.[79,80]
An in e es ing applica ion o he use o SRO is he de-
elopmen o cellula sys ems o in i o con inuous di ec
e olu ion.[81]Thus, using his sys em, i was es ablished a syn-
he ic o hogonal eplica ion sys em in E. coli ha allows o ac-
cele a ed e olu ion[82]; o each his objec i e, he esea che s de-
signed a mu an o hogonal DNA polyme ase ha does no copy
he bac e ial genome and selec i ely inc eases he mu a ion a e
o he o hogonal eplicon.
11.2. The WLO (Wei d Li ing O ganisms)
Among all he new syn he ic o ganisms, he WLO ep esen s
a he e ogeneous g oup o wei d li ing c ea u es, which a e de-
signed and c ea ed by combining non-biological echnologies like
AI and biological echniques such as emb yo manipula ion o
molecula bioenginee ing. The fi s membe o his g oup o
biza e o ganisms we e he “xenobo s”, a kind o li ing obo
designed using an AI e olu iona y algo i hm o p edic which
o ganisms could deploy use ul asks and build om emb yonic
cells o he og Xenopus lae is.[83]Xenobo s a e like minia u e ma-
chines made om li ing emb yonic og cells ha spend a li le
o e a week c awling o swimming a ound a Pe i dish be o e
disin eg a ing (as hey do no ea , hei li espan is sho ). The
AI p og am e ol es g oups o og cells, based on hei shape,
o pe o m any ask o in e es o he scien is s. These s ange
c ea u es sel - eplica e in an unp edic ed way ne e been seen
in na u e, e y diffe en om wha we know in o he euka yo ic
o ganisms.[84]
Ano he membe o he WLOs comple ely diffe en om
he p e ious one is a hyb id biocompu e buil by combining
labo a o y-g own human b ain issue wi h con en ional elec-
onic ci cui y; his hyb id sys em, wi h he name “B ainowa e”,
can comple e asks such as oice ecogni ion.[85]To make he hy-
b id sys em, he esea che s also used an AI ha dwa e app oach,
hey placed a single o ganoid on o a pla e con aining housands
o elec odes, o connec he b ain issue o elec ic ci cui s. To
es he capabili ies o b ainowa e, he sys em was employed o
do oice ecogni ion by aining he sys em wi h eco dings o
people speaking. Among o he po en ial applica ions, his s udy
opens he possibili y o c ea ing biological compu e s.
Resea ch wi h xenobo s, b ainowa e sys em, and o he biza e
c ea u es gene a ed by he combina ion o AI and biological ech-
niques could be e y beneficial o he u u e, o example, o
p og am hese biological en i ies o decon amina ion asks o
o egene a i e medicine. Xenobo s and b ainowa e a e jus he
beginning o WLO, bu I am con inced ha he e will be mo e
awesome syn he ic li ing sys ems coming soon.
11.3. The SCS (Syn he ically Cellula Sys ems)
The e m SCS includes all syn he ic (some imes e e ed o by he
e m a ificial) cellula sys ems c ea ed in he labo a o y. I con-
sis s o wo classes: LSC (Li ing Syn he ic Cells), which e e s o
li ing cells o ally c ea ed in he labo a o y ( he e a e no mem-
be s o his ca ego y ye ), and ACC (A ificially C ea ed Cells) o
ILS (Incomple e Li ing Sys ems), which a e cell-like s uc u es o
minimal cells ha mimic one o mo e cellula unc ions; I keep
he name ACC because i appea s equen ly in he specialized
li e a u e al hough in no case a e a ificial cells bu pseudo-cells
ha a e capable o ca ying ou some cellula unc ion bu canno
be conside ed li ing sys ems.
LSC would be hose li ing cellula sys ems ha ha e been c e-
a ed om sc a ch in he labo a o y, ollowing a bo om-up ap-
p oach, i.e., assembling all he undamen al o ganic and ino -
ganic componen s o a cell wi hin a memb ane, hus gene a ing
a li ing sys em ha has, a a minimum, a genome, a cy oskele-
on, and a basic me abolism sufficien o ob ain ene gy and build
new molecules o g ow.[86,87]Once his goal was achie ed, he
nex s ep would be o ge his p imi i e li ing sys em o ep o-
duce and e ol e. F om ha poin on, cellula complexi y could be
inc eased a bo h he subcellula and mul icellula le els. How-
e e , scien is s ha e no ye succeeded in c ea ing his minimal
cell in he labo a o y, al hough good s eps a e being aken in his
di ec ion. A significan ad ance was he in oduc ion o wo ypes
o bac e ia in memb ane- ee d ople s, leading o he o ma ion
o an a ificial cell wi h a unc ional and composi ional complex-
i y eminiscen o li ing cells.[88]Despi e he echnical difficul ies
in c ea ing a iable cell, i is e y likely ha in he coming yea s
o decades, scien is s will succeed in c ea ing li e in he labo a-
o y and o his eason, I ha e included in he classifica ion o
“Syn he ic O ganisms” he LSC wi hin he SCS. The c ea ion o
li e om inanima e ma e , besides opening a new uni e se o
syn he ic biology, will help us o sol e he g ea mys e y o biol-
ogy, which is none o he han he o igin o li e and he beginning
o he e olu iona y p ocess.[89]
When we e e o ACC o ILS, he fi s hing o say is ha since
he concep o a ificial cells was p oposed in 1957, he e ms “a -
ificial cells” and “syn he ic cells” ha e been used in e change-
ably, wi hou he e being a p ecise defini ion o hem.[90]He e I
use he e m “a ificial” because i is he mos used e m in he
li e a u e on he subjec . ACC o ILS en i ies (also known as min-
imal cells) a e enginee ed encapsula ed pa icles ha can be en-
dowed wi h a ious unc ions by inco po a ing bioac i e ma e i-
als, such as DNA, RNA, and p o eins, wi hin a memb ane.[90,91]
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An example o his echnology is he s a egy o assemble biocom-
pa ible cell-sized hyd ogel-based a ificial cells wi h a a ie y o
diffe en embedded unc ional sub-compa men s, which ac as
enginee ed syn he ic o ganelles.[92]The cons uc ion o a ificial
cells has g ea po en ial in he s udy o undamen al biological
ques ions such as example, he o igin o li e o he o ganiza ion
o cells, and also o use in applica ions ela ed o disease ea -
men and bio echnology.[90,93,94]
12. A-Li e Fo ms
As I men ioned ea lie , he aim o A-li e is o design and an-
alyze sys ems and p ocesses ela ed o na u al li e using com-
pu e modeling simula ions, obo ics, and biochemis y.[12]How-
e e , biological sys ems classified wi hin we A-li e could well be
conside ed as belonging o he field o syn he ic biology. F om
his s andpoin , he e a e only wo diffe en ypes o A-li e: so
A-li e ha e e s o compu a ional modeling and simula ion o
li elike beha io s, and ha d A-li e, which is ela ed o physical
obo s o a i ac s made o me al and plas ic, including medical
nano obo s defined as un e he ed nanos uc u es ha con ain an
engine o can ans o m di e se ypes o ene gy sou ces o me-
chanical o ces and pe o m a medical ask (Kong e al. 2023).
So and ha d A-li e o ms a e no li ing en i ies because hey
do no mee all he equi emen s o be conside ed li ing, jus as
a fligh simula o is no an ai plane o a pho o o a landscape a
angible eali y.[1]The so and ha d A-li e o ms ha e no hing
equi alen o gene ic ma e ial, a e no based on ca bon biochem-
is y, and canno adap and e ol e in esponse o changes in he
en i onmen , whe eas li ing sys ems ha e a modifiable gene ic
p og am, can in e ac wi h hei en i onmen , and adap o new
ci cums ances, and consequen ly can e ol e o gi e ise o new
species. These en i ies always depend on hei human designe ,
hey canno e ol e by hemsel es because o chance and na u al
selec ion. A compu e p og am o a sophis ica ed obo can ne e
be a li ing sys em because he momen i becomes a li ing being
i ceases o be a p og am o a obo . None heless, al hough so
and ha d A-li e a e no o ganic en i ies in which he i al p ocess
akes place, hey y o imi a e he li ing o design algo i hms o
sys ems ha could e en ually ha e a biological fi .
13. Concluding Rema ks
Fi s : The new biodi e si y. In gene al, when alking abou biodi-
e si y, e e ence is always made o he a ie y o p oka yo ic and
euka yo ic species ha make up ecosys ems, bu i uses and syn-
he ic o ganisms a e no men ioned. This should no be he case
because he e olu iona y ela ionship o i uses wi h hei na u-
al hos s and hei ole in ecosys ems is unques ionable and be-
cause syn he ic o ganisms can also colonize ecosys ems and e en
hyb idize wi h hei na u al “ ela i es”. I ha e no doub ha u-
u e s udies on e olu ion, biodi e si y, and ecology will ake in o
accoun he c ea u es belonging o he Li hbea domain because
hei ela ionship wi h o he li ing beings on he plane will be
inc easingly in ense.
Second: The unp edic abili y o he unknown. In he 21s cen-
u y, we a e aced wi h a g owing box o biological su p ises ha
a e he esul o eno mous p og ess in biology and new echnolo-
gies. These new biological en i ies may be e y use ul in he u-
u e o medical, en i onmen al, o indus ial pu poses, bu hey
also gene a e new dange s de i ed om he unp edic abili y o
he unknown.[14]We will ne e be ully ce ain o he ou come
and consequences o he c ea ion o a new syn he ic li ing being.
E en i he unknown could become la gely p edic able, he e will
always be a p inciple o unce ain y, as is he case wi h he p o-
cesses o he suba omic wo ld.
Thi d: E olu ion ha e ol es. S. Newman,[95]in an in e es ing
eflec ion on he inhe en o ms and he e olu ion o e olu ion,
a gues ha “Once a no el kind o biological ma e has been con-
s i u ed, e olu ion is channeled in new, p e e ed di ec ions, ….”.
In his di ec ion, i is possible o specula e ha new ules may
appea in he e olu ion o some o he syn he ic li ing beings
because hei c ea ion is no he esul o a na u al p ocess (i
has no been es ed by na u al selec ion), bu o di ec changes
in he gene ic p og am o he de elopmen o new syn he ic be-
ings. Pe haps he bes e idence o his so a is he xenobo s, be-
cause og cells, eleased om hei na u al de elopmen al pa h-
way, a e o ganized in dis inc ly un- og-like ways, hey clus e ed
in o sphe ical clumps ha beha ed like iny o ganisms. Anyway,
in my opinion, in o de o y o p edic he e olu ion o syn he ic
o ganisms, a leas ou ac o s mus be aken in o accoun : i) he
p ocess o c ea ion o he syn he ic o ganism because i will affec
bo h i s in e nal dynamics and i s ela ionship wi h he en i on-
men ; ii) he unp edic abili y o he unknown o , in o he wo ds,
he eme gence o new ules go e ning he e olu ion o syn he ic
o ganisms; iii) he influence o he laws o physics and chemis y,
om which li ing ma e canno escape; i ) he p inciple o inex-
o abili y ha says “ hings a e so because hey mus be so” and
ha applied o syn he ic o ganisms ells us ha i he syn he ic
o ganism wan s o fly i will need wings, ha i i wan s o g ow
i mus eed i sel , o ha glucose will be con e ed in o py u a e
unless we ha e in oduced changes in he glycoly ic enzymes.[96]
Fou h: Playing Gods ( he men ion o God has no eligious
componen bu a me apho ical one). Be o e he ad en o he bio-
logical e olu ion, he abili y o design and c ea e new li e was he
“exclusi e powe ” o he Gods, bu now we ha e he capaci y o
con ol ou own e olu ion and ha o o he species, and o man-
u ac u e new li ing beings wi h cha ac e is ics some o which we
canno e en imagine. Tha is why i is e y impo an a his poin
o se e hical limi s, o es ablish legal ules ha , wi hou mu i-
la ing scien ific p og ess, do no allow he c ea ion o biological
abe a ions o mic obial weapons o mass des uc ion.
Fi h: Ques ions in he ai . The ad ances in molecula biology,
compu e echnologies, and biological enginee ing ha make
his e olu ion possible aise many ques ions o which we do
no ye ha e a clea answe . Le me gi e some examples. I o -
ganisms wi h an al e ed gene ic code o syn he ic genome we e
eleased in o he wild, could hey hyb idize wi h hei na u al el-
a i es and e en ually displace hem by aking hei place in he
ecosys em? Wha would happen i a syn he ic pa hogenic mi-
c oo ganism could escape om he labo a o y and in ec human
popula ions? Could la ge-scale cul i a ion o gene ically mod-
ified plan s displace wild species and cause i e e sible dam-
age o he ecosys em? Wha would happen i xenobo s o o he
s ange li ing beings in aded ou en i onmen ? And so on and so
o h. We ha e o find a balance be ween scien ific p og ess, he
sa e y o people, he main enance o ecosys ems, and he e hical
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p inciples ha ell us ha no e e y hing goes o he sake o sci-
en ific success.
Conflic o In e es
The au ho s decla e no conflic o in e es .
Keywo ds
a ificial Li e Fo ms, li e concep , li hbea, syn he ic o ganisms, ee o li e,
i uses
Recei ed: Decembe 11, 2023
Re ised: Feb ua y 9, 2024
Published online:
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