Human in vitro eugenics: close,yet far awayFlávio Guimarães da Fonseca,1 Daniel Mendes Ribeiro,2

Nara Pereira Carvalho,2 Brunello Stancioli3

The article on human in vitro eugenicsby Sparrow is provocative and pertinent.1

Nonetheless, practical limitations to thetechnique of creating human gametesfrom stem cells have not been considered.Those limitations are relevant as theylead to ethical complications of highermagnitude than those presented in thepaper.

One practical limitation to the tech-nique is that, no matter how a pluripo-tent cell is created, it is still a diploidcell. In order to make gametes out ofsuch cells, they must be induced toundergo meiosis, which will turn theminto haploid cells. Only haploid gametescould fuse to generate a true zygote.Mitosis is distinct from meiosis; in theformer, segregation of DNA is equalthroughout all cell generations, but thisdoes not apply to the latter. In meiosis,heterozygous genes segregate differentlyto form different gametes. Moreover,numerous other processes become acti-vated during meiosis in order to providethe individual with the largest possiblearray of genetically diverse gametes.Processes such as homologous recombin-ation and crossing-over are quite frequentduring meiosis, causing small pieces ofDNA to be exchanged among chromo-somes.2 Mammalian spermatogenesis, forinstance, is divided into three phases:first, primitive diploid germ cells undergomitotic divisions to increase theirnumbers; next, they undergo meiosis toproduce haploid spermatids; and, finally,they differentiate into true gametesthrough a number of cell modificationsthat turn them into fully mobile sperm-atozoa. In this last phase there are nofurther divisions, only differentiation.3

Indeed, fully mature gametes are neithercultivable nor cloneable as they cannotundergo mitosis. It would therefore bevirtually impossible to screen for a single

gamete with the desired genetic traitwithout destroying it in the process, thusmaking it useless for any downstreamprotocol. This limitation would have tobe overcome if the technique is to beused for genetic improvement.Another important constraint of in

vitro eugenics is that the shortening ofgenerations—a possibility raised by theauthor as a way to study the presentationof genetic disorders—may have a signifi-cant impact on how a disease manifestsitself. The author acknowledges that theimpact of multiple gene interactions andthe environmental role in the phenotypeof an experimental subject may havebeen neglected in discussions promptedby in vitro eugenics. Nonetheless, a thirdimportant aspect may have goneunnoticed. Some diseases are not only aresult of multiple gene interactions or ofenvironmental pressure, but also a resultof some types of cell and tissue inter-action caused by biological ageing. As weage, genes are turned on and off, whichleads to growth and maturation of thebody. This is mostly achieved by the pro-duction of chemicals—mainly hormones—that work as a way of communicationbetween cells. Many genetic disordersevolve only after a certain age when hor-mones and chemicals are produced andset in motion the physiological onsetsthat generate a disease condition. Thisgoes beyond gene interaction within asingle cell and is related to the complexinteractions that take place within theorganism as a whole. All this complexnet of tissue-to-tissue cross-talking willsimply not happen if generations areshortened down to the embryogenic levelbefore the next generation starts fromcells of the previous one. Thus, aftersomething like 20 in vitro generations,will a disease manifest in the 21st subjectas it would after 20 real generations? Orwill it simply manifest in the second gen-eration after the study began? In otherwords, can we really consider that therewere 20 generations between the two ter-minal ones? Even in the microcosmoscreated by the multiple in vitro genera-tions prospect, problems may arise fromthe fact that the next generation in line isderived from cells taken from a simple

mass of embryo cells and not from amore developed organism. Again, takingthe mammalian spermatogenesis as anexample, it is agreed that the process ofgamete-making is regulated by the infor-mation contained in the cell undergoinggenesis and also by paracrine, juxtacrineand endocrine pathways.3 This meansthat surrounding cells and tissues areessential for spermatogenesis, and thesewill simply not be there during theprocess of gamete derivation from pluri-potent embryonic cells.

There is no doubt that the creation ofgametes from somatic pluripotent cellsand the possibility of multiple generationtesting in a short time frame are potenttools to study genetic segregationthroughout the generations. Patterns ofhow genes are segregated among gametes,how they would become imprinted on thepopulation and many other interestingquestions could be answered by multiplein vitro generation studies. In this context,would it be possible to study the behav-iour of disease-related mutated genesalong consecutive in vitro generations? Itis tempting to speculate that the identifica-tion of patterns of dispersion of geneticdisorders in vertical studies would be feas-ible. Still, the final phenotypic result ofsuch studies would always have to rely onbringing an embryo to term at somepoint. Even then, there is always the riskthat, while scientists focused their sightson a single gene or a limited group ofgenes, millions of other gene interactionsmay have happened. How that wouldaffect the desired trait or the whole fitnessof the subject is difficult, if not impos-sible, to foresee. It is relatively acceptableto experiment with this in laboratory miceor even in farm animals as a way toimprove their genetic attributes. But therisks are far too great—and unknown—topursue this in humans.

Practical limitations of the techniquetherefore lead to much bigger ethical con-undrums than the ones pointed out bySparrow. The technique would onlyachieve a level of desirable success andreliable data, according to scientific stan-dards, if and when the human embryosproduced are brought to term. The cre-ation of mature humans past the embry-onic stage following the presentedtechnique seems to be far from being eth-ically and socially acceptable.

Contributors BS came up with the idea ofwriting this commentary and, following discussionsbetween all the authors, drew up a general sketch ofwhat was to be written. FGdF was responsible forresearching and writing the larger part of the text

1Microbiology Department, UFMG, Belo Horizonte,Minas Gerais, Brazil; 2Law Department, UFJF,Governador Valadares, Brazil; 3Law School, UFMG,Belo Horizonte, Minas Gerais, Brazil

Correspondence to Brunello Stancioli, Rua BenjaminFlores, 280, 700, Santo Antônio, Belo Horizonte, MinasGerais cep 30350-240, Brazil; brunellostancioli@gmail.com

da Fonseca FG, et al. J Med Ethics Month 2013 Vol 0 No 0 1

Response JME Online First, published on August 13, 2013 as 10.1136/medethics-2013-101674

Copyright Article author (or their employer) 2013. Produced by BMJ Publishing Group Ltd under licence.

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regarding issues surrounding human spermatogenesisand epigenetics, and providing the references for theremarks on the subject. BS and DMR were responsiblefor drafting the (brief ) ethical commentaries concerningthe practical limitations of in vitro breeding of humangametes. NPC and DMR, under supervision by BS, wereresponsible for reporting and structuring the argumentsand revising the language for the final draft. FGdF andBS are responsible for the overall content asguarantors.

Competing interests None.

Provenance and peer review Commissioned;internally peer reviewed.

To cite da Fonseca FG, Ribeiro DM, Carvalho NP,et al. J Med Ethics Published Online First: [pleaseinclude Day Month Year] doi:10.1136/medethics-2013-101674

Received 26 June 2013Accepted 23 July 2013

▸ http://dx.doi.org/10.1136/medethics-2012-101200

J Med Ethics 2013;0:1–2.doi:10.1136/medethics-2013-101674

REFERENCES1 Sparrow R. In vitro eugenics. J Med Ethics. Published

Online First: 4 Apr 2013. doi:10.1136/medethics-2012-101200.

2 Krejci L, Altmannova V, Spirek M, et al. Homologousrecombination and its regulation. Nucleic Acids Res2012;40:5795–818.

3 Chocu S, Calvel P, Rollada AD, et al. Spermatogenesisin mammals: proteomic insights. Syst Biol Reprod Med2012;58:179–90.

2 da Fonseca FG, et al. J Med Ethics Month 2013 Vol 0 No 0

Response

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doi: 10.1136/medethics-2013-101674 published online August 13, 2013J Med Ethics

 Carvalho, et al.Flávio Guimarães da Fonseca, Daniel Mendes Ribeiro, Nara Pereira Human in vitro eugenics: close, yet far away

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