Mitochondrial replacement techniques and Mexico's rule of law: on the legality of the first maternal spindle transfer case

Abstract News about the first baby born after a mitochondrial replacement technique (MRT; specifically maternal spindle transfer) broke on September 27, 2016 and, in a matter of hours, went global. Of special interest was the fact that the mitochondrial replacement procedure happened in Mexico. One of the scientists behind this world first was quoted as having said that he and his team went to Mexico to carry out the procedure because, in Mexico, there are no rules. In this paper, we explore Mexico's rule of law in relation to mitochondrial replacement techniques and show that, in fact, certain instances of MRTs are prohibited at the federal level and others are prohibited at the state level. According to our interpretation of the law, the scientists behind this first successful MRT procedure broke federal regulations regarding assisted fertilization research.


INTRODUCTION
News of the first baby born after a mitochondrial replacement technique (MRT; specifically maternal spindle transfer [MST]) broke on September 27, 2016 and, in a matter None of the funds made available by this Act may be used to notify a sponsor or otherwise acknowledge receipt of a submission for an exemption for investigational use of a drug or biological product under section 505(i) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(i)) or section 351(a)(3) of the Public Health Service Act (42 U.S.C. 262(a)(3)) in research in which a human embryo is intentionally created or modified to include a heritable genetic modification. Any such submission shall be deemed to have not been received by the Secretary, and the exemption may not go into effect. 7 The former, of course, affects MRTs in the creation of female embryos, as mitochondria are only maternally transmitted (as will become clear next). On the other hand, the wording of the Bill does not rule out the creation of male embryos, who do not transmit mitochondria to further generations. Even if this is so, a spokesperson of the FDA has said that 'human subject research utilizing genetic modification of embryos for the prevention of transmission of mitochondrial disease cannot be performed in the United States in FY [fiscal year] 2016'. 8 Thus, MRTs have effectively hit a road block in the USA. 9 Additionally, it is important to bear two things in mind. First, no US federal legislation explicitly addresses human genetic modification. Second, in the USA, the Dickey-Wicker Amendment prohibits the use of federal funds for the creation of human embryos for research, or for research that results in the destruction of human embryos: (1) the creation of a human embryo or embryos for research purposes; or (2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero under 45 C.F.R. 46.208(a)(2) and 42 U.S.C. 289g(b). 10 It seems that all of these regulatory issues, in addition to the FDA's actions when a 'similar' procedure (cytoplasmic transfer 11 ) was conducted in the USA in the recent past, prompted Zhang to carry out the procedure in Mexico. 12 Adashi, Preventing Mitochondrial DNA Diseases: One Step Forward, Two Steps Back, 316 JAMA 273-274 (2016). 10 Bob Livingston, H.R.2880, 104th Congress (1995ffi 1996: BALANCED BUDGET DOWNPAYMENT ACT, I Sec. 128 (1996), https://www.congress.gov/bill/104th-congress/house-bill/02880 (accessed Oct. 3, 2016). 11 In cytoplasmic transfer, cytoplasm from a donor egg is transferred into a second egg to make up for a presumptive 'ooplasmic deficiency'. This technique was indented to help women who had experienced repeated poor embryo development and implantation failure. Jason A. Barritt  regulated, if at all, and because Zhang's fertility clinic has two branches there: one in the State of Mexico City and the other in the city of Guadalajara, within the state of Jalisco.
The procedure was carried out in the Guadalajara branch. Unfortunately, Zhang was quoted in the publication that broke the news as stating that he and his team went to Mexico because, in Mexico, 'there are no rules'. 13 Zhang was most likely referring to the fact that, in Mexico, MRTs are neither specifically regulated nor specifically forbidden; but even if this was his intending meaning, the media has since repeated ad nauseam that, in Mexico, there are no laws governing MRTs and assisted reproduction. Against this background, in this paper we set out to examine MRTs in the context of Mexico's rule of law. Specifically, we explore whether Mexican law prohibits either of the two MRTs: MST and pronuclear transfer (PNT). This research is important in terms of regulatory background given that the first successful instance of MST occurred in Mexico and it is feasible that Zhang's team-or another team-will consider carrying out either this procedure or PNT,in Mexico again. 14 In the first section of the paper, we present a brief account of mitochondrial DNA diseases and MRTs (if you are familiar with these topics then you can skip ahead to the second section). We explain how these techniques are carried out and describe two important characteristics of them. In the second section, we explore Mexico's rule of law in regard to MRTs. As stated above, we descriptively examine the legal status of MST and PNT. 15 First, we very briefly describe Mexico's political composition and examine whether Mexico's highest national law, the Political Constitution of the United Mexican States (hereafter the Federal Constitution), specifically protects life from the moment of conception or fertilization. 16 Secondly, we investigate the legality of MRTs from the perspective of federal laws. Thirdly, we identify those states in which local laws 13 Hamzelou, supra note 1. 14 Two things bear noticing. First, many media headlines have claimed that the baby born after MST was the first baby to have been intentionally produced with genetic material from three persons. Though this makes for a catchy headline, children were produced with genetic material from three persons in the late 1990s after ooplasmic transfer. C. A. Brenner et al., Mitochondrial DNA Heteroplasmy After Human Ooplasmic Transplantation, 74 FERTIL. STERIL. 573-578 (2000). Second, and most important, after this paper was accepted for publication Alejandro Chavez-Badiola, the director of New Hope Fertility Center in Mexico, announced that they are planning to use MST at least 20 times in the first half of 2017. Michael Le Page, Mexico Clinic Plans 20 ' Three-Parent' Babies in 2017New Scientist (2016, https:// www.newscientist.com/article/2115731-exclusive-mexico-clinic-plans-20-three-parent-babies-in-2017/ (accessed Dec. 12, 2016). 15 Although it is an important topic, in this paper we will not discuss the legal status of surrogacy in Mexico or its regulation through different state level civil codes-statutory law-in places such as Tabasco and Sinaloa. 16 (accessed Oct. 4, 2016). For an analysis of how the jurisprudences of the Inter-American Court of Human Rights have, historically, interacted with the protect human life from the point of conception and fertilization, and investigate how MRTs interact with such local laws. We pay particular attention to the state of Jalisco, given that it was there that the MST was carried out. Fourthly, we examine MRTs in terms of Mexican laws regulating both human genome modification and human genetic engineering.
In the third section of the paper, the conclusion, we briefly present our main points and explore how Zhang's team's actions have affected the assisted reproduction debate in Mexico. Specifically, we discuss how their actions have helped those who wish to pass federal legislation to prohibit MRTs, and that would restrict access to assisted reproduction.
Before moving to the next section, we clarify that this paper does not engage with the ethics of MRTs 17 or how they should be regulated on an international level. 18 Although both authors find that carrying out MRTs is, in principle, ethically permissible-one of the authors has written on the ethical permissibility of MRTs and the other on the importance of embryo and stem cell research for unmet health needsthe focus of this paper is on MRTs and Mexico's rule of law.

MITOCHONDRIA 19
All eukaryotic organisms, humans included, possess a double membrane-bound organelle called mitochondria, which resides in the cytoplasm. This organelle, among other things, produces the energy cells need to work properly. Two important characteristics of mitochondria are that they are solely maternally inherited 20 and that they possess their own DNA, which, again, is located outside the cell's nucleus. Whereas nuclear DNA accounts for 99.9 per cent of total human DNA, mitochondrial DNA (henceforth mtDNA), with its 37 genes, accounts for the other 0.1 per cent. 21 Given that mitochondria are responsible for generating the energy cells need to work properly, it is not surprising that when they do not work as they should there may be adverse effects on human health, ranging from mild to devastating in their severity. Mitochondrial diseases are caused by the inadequate function of mitochondria. These diseases can occur because of problems within the mtDNA, itself, or because of the effect of the nuclear DNA on mitochondrial function. 22 In this paper, we will only focus on problems related to the function of mtDNA, itself.
Roughly speaking, mitochondrial DNA diseases (henceforth mtDNA diseases) occur when enough mitochondria with deleterious DNA mutations exist for the production of energy to be insufficient for cells to work properly. Let's remember that each cell has many mitochondria. Deleterious mutations can (a) occur spontaneously during mtDNA replication, (b) be inherited, or (c) both. These mutations can occur across all mitochondrial genomes-a condition referred to as 'homoplasmy'; or they can only occur in some mitochondrial genomes-a condition referred to as 'heteroplasmy'.
Women with homoplasmic deleterious mutations will always pass this condition to their children, and those with heteroplasmic deleterious mutations will pass a mix of unhealthy and healthy mitochondria to their children. The severity of the mtDNA disease and whether it will manifest at all, in children of heteroplasmic women, depends on the type of mtDNA mutation and the load of deleteriously mutated mitochondria. Prediction on this outcome is difficult, since mitochondria are not inherited in a Mendelian manner; rather, their inheritance depends on a phenomenon called the 'mitochondrial DNA genetic bottleneck 23 '.
It must be clear that, up to this point, we have discussed mtDNA diseases, in plural, because such diseases cannot be categorized in a singular fashion. Deleterious mutations in mtDNA can cause Leigh's syndrome, deafness, blindness, stroke, dementia, major organ failure, heart failure, and Leber's hereditary optic neuropathy, among other conditions. 24 The UK Department of Health asserts that 1 in every 6500 children born in the UK has an mtDNA disease. 25 As there is presently no cure for mtDNA diseases, women who have them (and are aware that they have them) and want to have genetically related kin face a difficult reproductive choice. Homoplasmic women know that if they reproduce naturally, all of their children will inherit their homoplasmic condition and will probably end up with a clinical manifestation of the disease. Heteroplasmic women, on the other hand, know that it is probable that their children will possess a deleterious mutant load that could cause the disease to manifest. Until now, women with mtDNA diseases who want to have genetically related children have had to choose between natural procreation or, where available, preimplantation genetic diagnosis (PGD)-with the latter option only available to heteroplasmic women.
The idea behind using PGD is that physicians are able to select an embryo that possesses no mutant load, or one that possesses a mutant load so small that the clinical manifestation of the disease will not occur. 26 A problem with this approach is that it does not work for homoplasmic women, as implied above, and that, in the case of heteroplasmic women, it only works when there is enough data on the specific mtDNA mutation. This suggests that PGD is not useful for mutations that are uncommon or private. It must be obvious that there are other reproductive options for women affected by mtDNA diseases: egg and embryo donation. However, these forgo the maternal genetic link that is of paramount importance to some.
Another option (which was merely theoretical until recently) is for women to opt for one of two recently developed techniques that would allow them, if successful, to have children free from their mtDNA disease. These techniques are maternal spindle transfer and pronuclear transfer, and these have been jointly called 'mitochondrial 23 'During the production of primary oocytes, a selected number of mitochondrial DNA (mtDNA) molecules are transferred into each oocyte. Oocyte maturation is associated with the rapid replication of this mtDNA population. This restriction-amplification event can lead to a random shift of mtDNA mutational load between generations and is responsible for the variable levels of mutated mtDNA observed in affected offspring from mothers with pathogenic mtDNA mutations' Robert W. Taylor  replacement techniques'. 27 It is important to highlight that these techniques only tackle mtDNA diseases. 28 In PNT, assisted reproductive techniques (ARTs) are employed to create two zygotes. One is created with the intending parents' gametes (or the intending mother's egg and a donor's sperm). The second is created with an egg that has been donated from a woman 29 without an mtDNA disease, and the intending father's (or donor's) sperm. After fertilization occurs, the nuclear material of the egg and sperm are enclosed in different membranes, called the male and female pronuclei. These pronuclei are removed from both zygotes during the first 24 hours and prior to their fusion. The pronuclei that include the donor's nuclear material and the enucleated cell that was originally produced with the intending mother's oocyte are discarded. The intending parents' pronuclei are then transferred to the enucleated zygote that was produced with the donor's egg. At this point, the intending parents' nuclear material is housed in a cell possessing healthy mitochondria and is transferred into the intending mother or a surrogate. 30 In MST, oocytes are obtained from the intending mother and a healthy donor through ARTs. The chromosomes of both oocytes, which at the moment of cellular division (metaphase II) are found to one side of the oocyte in a spindle shape group, are removed. The donor's chromosomes and the intending mother's enucleated oocyte are discarded. Afterwards, the intending mother's chromosomes are transferred to the donor's enucleated oocyte. The reconstructed egg, with healthy mitochondria, is then fertilized in vitro and transferred to the intending mother or a surrogate. 31 Children born after PNT or MST will not have an mtDNA disease if during the procedures there was not enough carryover of deleteriously mutated mitochondria for the disease to clinically manifest. 32 In this case, the donor's healthy mitochondria will be passed to future generations when women born after MST or PNT reproduce using their own eggs.
T WO RELEVANT CHARACTERISTICS Two characteristics of MRTs are relevant in terms of law and regulation. The first is that both PNT and MST can be instances of either germline or somatic modifications. As stated above, PNT and MST affect the germline, in the sense that they are modifications that will be inherited by future generations if a female individual produced through them reproduces. However, both techniques are somatic modifications when a male embryo is selected for, in the sense that the modifications will not be inherited by future generations if the individual produced through them reproduces.
It is possible to both select the sex of the embryo that will be created and select the sex of the embryo that will be transferred to the mother or a surrogate. Through PGD one can choose the sex of the embryo that will be transferred. This means that if post-MST a female embryo and a male embryo are produced and we want to avoid modifications being passed down, we can identify the male embryo and transfer it. On the other hand, through sperm sorting we can choose a sperm with an 'X' or a 'Y' sex chromosome and thus select the sex of the embryo that will be created. This technique works prefertilization and also allows us, for example, to create only male embryos.
The second characteristic that is relevant for law and regulation is the difference between PNT and MST in terms of the time at which they occur. Whereas MST involves oocytes, PNT involves zygotes. In MST, the donor's oocyte is destroyed for the sake of the intending mother's oocyte. In PNT, however, an early embryo is destroyed for the sake of another early embryo. In moral terms, this difference is of paramount relevance for those who hold that human embryos possess the same moral status as human persons. This difference between PNT and MST is also important because, as we will see below, certain jurisdictions protect 'human life' from the moment of fertilization.

ME XICO
The United Mexican States, commonly known as Mexico, is a federal republic of 32 states. 33 The states' powers, at both the local and the federal level, are divided into executive, legislative, and judicial powers. At the federal level, the executive power falls to the President; the legislative power falls to the Congress of the Union (henceforth Congress), which is divided into two chambers: the Senate and the Chamber of Deputies; and the judicial power falls to the Supreme Court of Justice (henceforth the Supreme Court).
Mexico's highest law is the Federal Constitution and in it (Articles 39 to 41) the form of government and the integration of the Federal Republic is established. Each of the 32 states has a local constitution, but the Federal Constitution overrides lower sources of law at all times-and, from 2011, also international conventions related to human rights protections-and local constitutions must be aligned with the Federal Constitution's provisions.
The Supreme Court exercises constitutional control and plays an important role in interpreting the Federal Constitution. 34 It has the power to strike down any local law that contradicts or contests the Federal Constitution, and it can also pronounce itself in favor of the constitutionality of any challenged law. There are two ways to create jurisprudence, which is analogous to precedent/case law in common law systems. 35 The first is stipulated by the reiteration criteria. According to this criteria, rulings made by the Supreme Court and all federal judges and magistrates-which are called relevant resolutions-create jurisprudence when five relevant resolutions are ruled using the same line of legal reasoning. The second way to create jurisprudence is when eight of the eleven members of the Supreme Court agree on the main point of a particular relevant case. Jurisprudence of the Supreme Court is binding to all lower courts due to its hierarchy within the judicial system.

ME XICO'S RULE OF L AW AND ASSISTED REPRODUCTION
The Federal Constitution neither defines a human embryo nor expressly defends human life from the moment of conception or fertilization. Despite this, conservatives have tried to argue that human life is protected from its beginning under Article 1 of the Federal Constitution 36 : (...) Any discrimination based on ethnic or national origin, gender, age, disabilities, social status, health condition (...) or any other reason which attempts against human dignity and which is directed to either cancel or undermine people's rights and liberties is prohibited. 37 According to conservatives, abortion and the destruction of human embryos are an affront to the right to life and the human dignity of those destroyed or terminated. Thus, these practices are legally prohibited. Although the Supreme Court recently favored this interpretation 38 in a ruling regarding abortion due to severe congenital conditions, it established in its latest ruling (also regarding abortion) that: It is clear that from a plain reading of the Mexican Constitution, we did not explicitly find in any of its text the institution of a specific right to life, the value of life, or other expression that allows to determine that life has a specific normative protection through a prohibition or mandate directed at the state's authorities. 39 Diverging from previous rulings on abortion, where the focus was on civil law which protects the interests and rights of the unborn, in its latest ruling the Supreme Court favored women's reproductive rights over the life of the unborn and focused on the extent 35  Additionally, this ruling found that articles protecting human life that are in, or can be derived from, international declarations, covenants, and treaties of which Mexico is signatory do not expressly establish when life begins or the moment from which it should be protected. An exception to this finding is provided in Article 4 of the American Convention on Human Rights, of which Mexico is signatory. This article asserts that: 'Every person has the right to have his life respected. This right shall be protected by law and, in general, from the moment of conception. No one shall be arbitrarily deprived of his life'. 42 Although this article asserts that human life should, in general, be protected from the moment of conception, Mexico is not obliged to recognize this because the Mexican government made an interpretative declaration of that specific article at the moment of ratification. They considered the decision to protect life 'in general' from the moment of conception as one that should be taken by each individual state.
In relation to paragraph 1 of Article 4, [the Mexican government] considers that the expression 'in general' used in such paragraph does not constitute an obligation to adopt or maintain in force legislation that protects life 'from the moment of conception' since such matters belong to the reserved dominion of the States 43 At the federal level, the General Health Law 44 (a secondary piece of legislation) provides the legal definition of an embryo. Before commenting on this definition we will briefly elaborate on this law. The General Health Law regulates the right to the protection of health afforded to every person according to Article 4 of the Federal Constitution. In addition to the General Health Law, each state has its own health law. But, as described above, when there is conflict between a local health law and the General Health Law, the latter overrules the former.
It is reasonable to suppose that a legal definition of an embryo would appear in the section of the law dedicated to assisted reproduction. However, the General Health Law does not specifically regulate assisted reproduction. 45  A consequence of the lack of specific regulation concerning assisted reproduction is that, at the federal level, no organization or authority regulates, evaluates, and compiles information about the way in which ARTs are carried out in Mexico, or the persons who carry them out. 47,48 It also means, among other things, that there is no legal certainty about what kind of information should be collected for epidemiological and legal purposes, and the length of time that gametes and embryos should be stored. In terms of actual clinical practice, the Mexican Association of Reproductive Medicine and the Latin American Network of Assisted Reproduction (RedLara)-among other professional bodies-provide recommendations and regulations relating to the practice of assisted reproduction in Mexico. Nonetheless, clinics that offer assisted reproductive services follow their recommendations and regulations only on a voluntary basis.
At this point, it could be thought that, in terms of the General Health Law, there are no restrictions on MRTs in Mexico. But surprisingly, the Regulations of the General Health Law on Health Research include some directives that apply to MRTs. This regulatory document is an independent body of text (in the sense that it is not contained within the General Health Law) and, as its names suggests, further regulates certain aspects of the General Health Law. Article 56 of this regulation asserts that: Research on assisted fertilization will only be admissible when it is applied to solve sterility problems that cannot be solved otherwise [ Now, if a woman's eggs have mitochondria with deleterious DNA mutations such that the embryos produced with them will never be able to implant (making pregnancy impossible), then research on MRTs to solve this problem does not violate Article 56. This is because MRTs solve a sterility problem that cannot be otherwise solved. On the other hand, research on MRTs (ie research on assisted fertilization) for helping fertile women to have children without a mtDNA disease would violate Article 56. This is so because research on MRTs is not intended to solve sterility problems that cannot be solved otherwise.
At this point, we can conclude that-assuming this interpretation of the law is correct and with the information we possess about the case-Zhang's team violated Article 56 of this regulation. 54 They did so because their research on MST included a woman who could get pregnant and deliver a live baby. In other words, research on MST was not used to solve a sterility problem that could not be otherwise solved. The Regulations of the General Health Law on Health Research do not establish a specific sanction for the violation of this article; however, they do assert that sanctions for violations of these regulations will be established by 'the law', in this case the General Health Law.
Article 416 of the General Health Law asserts that violations to this law and its regulations (eg Regulations of the General Health Law on Health Research) will incur administrative sanctions. 55 In Article 417, these sanctions are outlined: (a) a warning with a subpoena, (b) a fine, (c) a temporal or definitive shutdown that can be partial 50 Article 40 section XI defines assisted fertilization as follows: 'That in which the insemination is artificial (homologous or heterologous) and includes in vitro fertilization'. Id. Now, in vitro fertilization is not defined in this law. However, it is reasonable to contend that reproductive practices that inherently include in vitro fertilization fall under the umbrella of assisted fertilization. 51 Sterility is defined, elsewhere, as the failure to achieve a clinical pregnancy after 12 months of regular unprotected sexual intercourse.  54 Someone could claim that Zhang's team's actions were a research step toward solving sterility problems that cannot be solved otherwise, and thus legal. Even when this might seem compelling, we contend that there is a strong reason to doubt that Zhang's team's treatment of the Jordanian couple was only a step in research toward solving mtDNA diseases that cause sterility problems that cannot be solved otherwise. This is that when the team was, repeatedly, asked about Mexican regulations they never made this important precision, even when a big part of the whole controversy has revolved around MRTs regulations. 55 CÁMARA DE DIPUTADOS DEL H. CONGRESO DE LA UNIÓN, supra note 46. or total, and (d) incarceration for up to 36 hours. 56 The health authorities determine which of the above apply in each specific case. If the authorities decide on a fine, then its amount is established in conformity with Article 422, and can go up to 16,000 times the minimum wage (which roughly equates to 61,953.64 US dollars). 57 Furthermore, another sanction of the General Health Law could apply to the violation of Article 56, depending on the fact if research on MRTs can be classified as research on human beings. It is true that carrying out MST does not equate to carrying out research on a human being; however, when we consider MST in conjunction with the woman who will be pregnant we realize that this research possesses a central human element, and thus could be constructed as research on a human being. Article 101 of the General Health Law dictates that persons carrying out research on human beings in contravention of this law or other applicable provisions (eg Regulations of the General Health Law on Health Research) are worthy of sanctions. 58 Now, if research on MRTs is considered research on human beings, then in this particular case a violation of Article 56 of the Regulations of the General Health Law on Health Research would engage Article 101 of the General Health Law. The sanctions for a violation of Article 101 of the General Health Law are found in Article 421, which states that those who violate Article 101 will receive a fine between 6000 and 12,000 times the minimum wage (which roughly equates to a fine between 23,271.83 and 46,543.66 US dollars). 59 These sanctions are meant to be applied by the Federal Commission for the Protection Against Sanitary Risks (COFEPRIS). 60 In conclusion, under our interpretation of the law and with the available information about the case, we can assert that Zhang's team broke the Regulations of the General Health Law on Health Research, and that it is very probable that they also broke regulations regarding research on human beings. This conclusion, obviously, stands in stark contrast to Zhang's team's statements about the legality of their research in Mexico.

ME XICO AND THE RIGHT TO LIFE
Another way in which we can elucidate the instances in which MRTs and certain applications of MRTs are legally prohibited in Mexico, in addition to the specifications in Article 56, is to shift our attention from federal laws and regulations to state laws and regulations. Doing so allows us to identify states with laws that protect life from the moment of fertilization. We can then determine which states legally permit PNT, because PNT involves the intentional destruction of a single cell human embryo and this would be prohibited under such laws. 61 At this point, let's remember two things: Mexico's Federal Constitution does not protect life from the point of conception or fertilization and laws protecting human life from the point of conception would not apply to PNT 56 Id. 57 Currency exchange rate calculated at 1 US dollar to 18.83 Mexican pesos (Oct. 10, 2016 63-78 (2012). 61 In these states, the destruction of surplus embryos after both MRTs would also be legally prohibited. State where MST was carried out. Purple, states where human life is protected from the moment of conception (ie implantation). Green, states where PNT is prohibited because human life is protected from the moment of fertilization. Orange, state where PNT is prohibited if the would-be-enucleated embryo is first created for a non-reproductive purpose.
(given that conception is understood as the moment at which implantation occurs, and the destruction of human embryos for PNT occurs prior to implantation). In Mexico, 18 local constitutions protect life from the point of conception or fertilization (see Fig. 1).
Interestingly, Jalisco is one of the states that constitutionally protects life from the moment of fertilization. In this way, it clearly diverts from the Federal Constitution: Article 4. (...) Likewise, the State of Jalisco recognizes, protects and underwrites the right to life of every human being, by expressively maintaining that from the moment of fertilization he is under the protection of the law and that he is reputed as born for all legal effects, until his natural death. 62 Let's remember that Zhang's team carried out MST in the city of Guadalajara, which is within the state of Jalisco. This means two things. First, if Zhang's team had carried out PNT (which they did not), then they would have broken this law. Secondly, if after MST they destroyed the other three aneuploid embryos, while in Jalisco, then these actions would have clearly violated Article 4 of the state's constitution. At this point, we do not know the embryos' fate. We do not know if they were destroyed, cryopreserved, or taken to another jurisdiction.
If Zhang's team were to declare that they intentionally destroyed the aneuploid embryos while in Guadalajara, or Jalisco, then we might question whether the state could try to prosecute them. Given that there is no precedent for this type of case (ie cases relating to MRTs), we must look to other cases in which persons have been prosecuted by the state for intentionally destroying embryos: abortion cases. Jalisco is among the most conservative states in Mexico and in addition to having laws that protect human life from the moment of fertilization it has a very punitive penal code in regard to abortion. Among Mexican states, Jalisco has one of the highest percentages of prosecution against women who abort, or who are suspected of having had an abortion.
Thirty-two women were prosecuted from 2007 to 2012 under such charges, and, of these, 25 were convicted. 63 Despite this, a person who intentionally destroys a human embryo in vitro while carrying out ARTs, or as part of ART research (eg MRTs), cannot be prosecuted under abortion laws. This is because Jalisco's penal code, Article 227, defines abortion as 'the death of the product of conception at any time during pregnancy'. 64 It should be obvious that without a pregnancy there can be no abortion.
Another option for the state would be to prosecute the intentional destruction of embryos as a homicide. 65 The state could follow this path because Article 213 of the state's penal code asserts that: 'From twelve to eighteen years in prison will be imposed to the person that takes the life of another one'. 66 And section I of Article 214 asserts that an injury will be considered fatal and thus sanctions of Article 213 will engage when: 'the death is due to the alterations caused by the injury to the interested organ or organs, or that death is due as immediate or determinate consequence of the injury'. 67 These articles could apply to cases of embryo destruction during PNT or after MST because, in Jalisco, a single cell embryo is, for all legal purposes, reputed as born from the moment of fertilization. Even if the embryos would die naturally if they were to be transferred to a woman, their intentional destruction could still be prosecuted since, in legal terms, their destruction would be akin to intentionally killing someone with a condition that will kill her in a couple of hours.
In conclusion, in Mexico, nine states prohibit PNT through laws protecting human life from the moment of fertilization. In Jalisco, specifically, the intentional destruction of human embryos could be prosecuted under criminal charges as homicide.

ME XICO AND GENOME MODIFICATION AND GENETIC ENGINEERING
In Mexico, no federal law specifically concerns human genetic engineering or human genome modification. The General Health Law has a section on The Human Genome 68 , but it simply addresses the gathering and use of human genetic information. As a matter of fact, this section of the General Health Law does not engage with human genome modification or human genetic engineering of any kind. 69 The only piece of federal legislation that directly addresses genetic engineering and genome modification is the 2005 Law on the Biosafety of Genetically Modified Organisms (GMOs). This piece of federal legislation was created with the intention of managing actual and possible risks related to the use and development of GMOs, in addition to promoting the development of this scientific area. Although this law regulates GMOs-and thus it is reasonable for us to expect to find in it regulations regarding human genetic engineering and human genome modification-it explicitly excludes humans from its oversight by means of its definition of GMOs. In Article 3, section XXI it asserts: Genetically modified organism: Any living organism, with the exception of human beings [emphasis added], that has acquired a novel genetic combination, generated through the specific use of techniques of modern biotechnology (...) 70 Thus, at the federal level, there is no law prohibiting human genetic engineering or genome modification at either the somatic or the germline level. Therefore, MRTs are not prohibited under this law. Although there is no federal law covering this ground, Mexico is signatory to international declarations that address the modification of the human germline. For example, Mexico is signatory of the Universal Declaration on the Human Genome and Human Rights, which explicitly addresses human germline modifications: whereas the General Health Law mainly imposes administrative sanctions. Article 154 of this penal code establishes that: Between two and six years in prison, disqualification, suspension for the same amount of time from working in posts, jobs or public commissions, profession or trade, will be imposed to those who: I. with different goals to the elimination or diminishment of grave diseases or maladies, manipulates human genes such that the genotype is altered; II. fertilize human oocytes for any goal different to human procreation; and III. create human beings by means of cloning or carry genetic engineering procedures for illicit ends. 71 It is clear that carrying out MRTs in the State of Mexico City in order to help women or couples have children without an mtDNA disease does not violate section I of Article 154-taking into account that Article 56 of Regulations of the General Health Law on Health Research should be followed. In terms of section II of this article, creating an embryo with the intention of later on enucleating it is prohibited. This means that PNT is prohibited when, during its procedure, an embryo is created for a non-reproductive purpose, as is the case when an embryo is created with the sole intention of later enucleating it. Interestingly, not all instances of PNT are prohibited under section II. PNT practices are legally permitted in the State of Mexico City if the would-be-enucleated embryos are first created for a reproductive purpose. For example, a couple going through 'normal' IVF could produce five embryos and end up with three surplus embryos if the first cycle results in a child. This couple could later decide to donate their three surplus embryos to a woman with an mtDNA disease who is considering PNT, supposing that the embryos have been cryopreserved at the right moment for PNT to be carried out. If doctors later enucleate these three embryos to carry out PNT, they would not violate section II, since the enucleated embryos were originally created for a reproductive purpose. Pointing out this caveat is important because we can now appreciate that in the State of Mexico City PNT is not absolutely prohibited. Additionally, the State of Mexico City does not protect life from the moment of conception or fertilization and does not explicitly prohibit the destruction of early embryos (see Fig. 1).
In conclusion, Mexico has no federal laws regulating human genome modification or human genetic engineering, and the international documents of which Mexico is signatory do not expressly prohibit human genome modification or human genetic engineering at the somatic or germline level. In the State of Mexico City, PNT is only prohibited when would-be-enucleated eggs are intentionally created for a non-reproductive purpose.
open to more experiments like Zhang's taking place. 74 Thus, Zhang's team's actions have, unwittingly, helped the conservative cause make a stronger case for poorly considered legislation to be passed in a developing country. 75 Further, and paradoxically, Zhang's team's actions have helped the case for passing legislation in Mexico that would legally prohibit MRTs, and which would certainly have economic effects on his fertility clinics in Mexico due to restrictions on who can access ARTs. In terms of research, for example, Article 71 bis 6 of the proposed amendments asserts that the creation of genetically modified embryos is prohibited; experimentation with or on embryos is prohibited; creation of embryos for non-reproductive ends is prohibited; transportation of sperm, oocytes or embryos out of the country is prohibited; and any kind of selection against disability is prohibited. 76 It is clear that while the birth of the first post-MST baby has prompted a discussion of MRTs in Mexico, it has also helped those who wish to bar MRTs and related practices from happening in the country.