research paper on cloning

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals

Cloning articles from across Nature Portfolio

Cloning is a method that is used to produce genetically identical copies of pieces of DNA, cells or organisms. Cloning methods include: molecular cloning, which makes copies of pieces of DNA; cellular cloning, which makes copies of a cell; and whole organism cloning. All cloning methods involve DNA and cell manipulation.

Latest Research and Reviews

Generation of Fel d 1 chain 2 genome-edited cats by CRISPR-Cas9 system

• Sang Ryeul Lee
• Kyung-Lim Lee
• Il-Keun Kong

Reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer

Somatic cloning of rhesus monkey has not been successful until now. Here, authors report epigenetic abnormalities in SCNT embryos and placentas and develop a trophoblast replacement method that enables them to successful clone of a healthy male rhesus monkey.

• Zhaodi Liao
• Jixiang Zhang

Insights from one thousand cloned dogs

• P. Olof Olsson
• Yeon Woo Jeong
• Woo Suk Hwang

Haploidy in somatic cells is induced by mature oocytes in mice

Yeonmi Lee, Aysha Trout, Nuria Marti-Guiterrez et al. examine different aspects of somatic cell haploidization in mouse enucleated oocytes. Their results provide further insight into generating oocytes carrying somatic genomes.

• Aysha Trout

shRNA transgenic swine display resistance to infection with the foot-and-mouth disease virus

• Haixue Zheng

Blastocyst formation, embryo transfer and breed comparison in the first reported large scale cloning of camels

• P. O. Olsson
• A. H. Tinson
• W. S. Hwang

News and Comment

Fda is the wrong agency to regulate genetically engineered animals.

• John J Cohrssen
• Henry I Miller

Author response to John Kasianowicz and Sergey Bezrukov

• David Deamer
• Mark Akeson
• Daniel Branton

Production of hornless dairy cattle from genome-edited cell lines

• Daniel F Carlson
• Cheryl A Lancto
• Scott C Fahrenkrug

Piglets cloned from induced pluripotent stem cells

• Liangxue Lai

Proteomics-directed cloning of circulating antiviral human monoclonal antibodies

• Sean A Beausoleil
• Roberto D Polakiewicz

Direct cloning of large genomic sequences

The discovery of an efficient mechanism of homologous recombination between two linear DNA substrates provides a new method for direct cloning.

• Ryan E Cobb
• Huimin Zhao

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

An official website of the United States government

Official websites use .gov A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

• Publications
• Account settings
• Advanced Search
• Journal List

Animal cloning and consumption of its by-products: A scientific and Islamic perspectives

Mohd izhar ariff mohd kashim, nur asmadayana hasim, diani mardiana mat zin, latifah amin, mohd helmy mokhtar, safiyyah shahimi, sahilah abd mutalib.

• Author information
• Article notes
• Copyright and License information

Corresponding author at: Center of Shariah, Faculty of Islamic Studies, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia. [email protected]

Received 2020 Apr 23; Revised 2021 Feb 3; Accepted 2021 Feb 8; Issue date 2021 May.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Islam is a religion that inspires its followers to seek knowledge continually and nurtures innovation, within the realms of Islamic rulings, towards an ameliorated quality of life. Up-to-date biotechnological techniques, specifically animal cloning, are involved in advancing society’s health, social, and economic domains. The goal of animal cloning includes the production of genetically modified animal for human consumption. Therefore, this research endeavoured to study animal cloning’s current scientific findings, examine the by-product of said process, and determine its permissibility in an Islamic context. This study employed descriptive literature reviews. Results concluded that animal cloning, especially in mammals, does not occur naturally as in plants. A broadly trusted and efficient animal cloning method is known as Somatic Cell Nuclear Transfer (SCNT), which includes three principal steps: oocyte enucleation; implantation of donor cells (or nucleus); and the activation of the embryo. Nevertheless, the limitations of SCNT, particularly to the Large Offspring Syndrome (LOS), should be noted. One of the forms of the application of animal cloning is in agriculture. From an Islamic perspective, determining the permissibility of consuming cloned animals as food is essentially based on whether the cloned animal conforms to Islamic law’s principles and criteria. Islam interdicts animal cloning when it is executed without benefiting humans, religion, or society. Nonetheless, if it is done to preserve the livelihood and the needs of a community, then the process is deemed necessary and should be administered following the conditions outlined in Islam. Hence, the Islamic ruling for animal cloning is not rigid and varies proportionately with the current fatwa.

Keywords: Islam, Modern biotechnology, Animal cloning, Somatic Cell Nuclear Transfer (SCNT), Food

1. Introduction

Islam urges one to seek knowledge and innovation to improve overall well-being and quality of life. Nevertheless, in recognising the sense of enhancing the quality of life, one must also ensure that their efforts comply with the Islamic rulings and not trigger adverse consequences, especially to humans. Modern biotechnology constitutes one of the key focuses of research in the last three decades. Since its conceptualisation, cloning has been a well-debated subject in addressing modern biotechnology issues in both the public and scientific fields ( Larijani and Zahedi, 2004 ). The swift scientific advancement of animal cloning has garnered considerable attention, which led to critical consideration and review of the process ( Fiester, 2005 , Zin et al., 2019 ). Modern biotechnology applications can be broadly identified in genetics, medicine; bioremediation, human cell clones; Genetically Modified (GM) crops, GM food, and animal cloning. The first successful cloning was conducted by a group of scientists at Roslin Institute, Scotland, in 1995, using two sheep, Megan, and Morag.

The following year, the same group of scientists used adult stem cells to clone Dolly. Presently, scientists are not only cloning various species of animals, but these advanced scientific techniques are also used for genetic modification (GM) purposes, such that in the production of transgenic animals ( Hasim et al., 2020 ). This process entails introducing a foreign gene into an animal’s genome to deliver desirable and economically significant characteristics in an animal. For instance, an experiment attended to produce a sheep that expresses a human gene resulted in the Factor IX protein in its milk, which can then be used to treat blood clots in humans with haemophilia ( Ibtisham et al., 2017 ). Similarly, transgenic sheep are also made to produce human alpha-1-antitrypsin, which can treat emphysema diseases ( McCreath, 2000 ). Other goals of cloning include the production of genetically modified animal organs to support human compatibility. Following the recognition of the numerous advantages of cloning and its capacity to serve various objectives, the agricultural sector has incorporated animal cloning into its practices to promote economic and environmental factors. Some typical transgenic methodology applications in agriculture comprise advanced milk production quality, improved disease resistance, and enhanced carcass composition to reduce environmental impacts ( Isa, 2013 ). In attempts to reduce the environmental impacts, scientists are also producing featherless chickens to reduce overall farming costs and pigs with a lower amount of phosphorous in their faeces ( Thomas, 2003 ). Scientists at Texas A&M University have also cloned a cow resistant to brucellosis ( Phillips, 2002 ).

US Food and Drug Administration (FDA) conducted extensive assessments to evaluate cloned animal food products’ safety. It was shown that there is no difference in the composition of food products produced from animal clones and their offspring in terms of food safety relative to conventionally bred animals ( FDA, 2008 ). Besides, a literature survey that analysed the composition, quality parameters, genotoxicity, and allergic reactions observed no differences in these parameters between meat or milk derived from cloned animals and their progeny from meat and milk of its nonclone counterparts ( Hur, 2017 ). No further evidence was shown that meat and milk from cloned animals pose a food safety risk. Thus, these findings were following the evaluations from the FDA.

The development of cloning technology has triggered severe concerns and garnered countless controversies surrounding ethical and religious perspectives ( Isa, 2013 ). This study concentrated its arguments based on Islamic rulings, as it is the official religion of Malaysia. Allah SWT said: And We have not sent you, [O Muhammad], except as a mercy to the worlds (al-Anbiyaa’, 21:107). This verse symbolises that Islam was sent down as a mercy to humankind, supporting our understanding that the basis of Islamic rulings considers society’s interest ( Samsudin et al., 2015 , Hasim et al., 2016 ). Consequently, modern biotechnology’s commercialisation and utilisation are also essentially dependent on the public’s perception and approval of stated technology ( Amin et al., 2009 ). This study analysed modern biotechnology, primarily about foods from cloned animals, in the scientific and Islamic context.

2. Animal cloning

2.1. natural cloning.

There are several methods of animal reproduction, including asexual and sexual reproduction. Asexual reproduction coexists with hermaphroditism and bisexual internal and external sex ( Benagiano and Primiero, 2002 ). Animals may reproduce through asexual means by budding in jellyfish, coral reefs, tapeworms; fragmentation in worms; and parthenogenesis in fish, insects, frogs, and lizards. Most animals that reproduce asexually do so through parthenogenesis, which is triggered during specific conditions. Parthenogenesis is a more effective form of breeding than sexual reproduction, as it enables faster exploitation of available resources ( Vajta and Gjerris, 2005 ). Nevertheless, mammalian asexual reproduction is not a naturally occurring phenomenon, despite the possibility of monozygotic twins (genetically identical) in mammals. Monozygotic twins are not considered clones as they are not the product of asexual breeding, and they differ from cloned animals, which only share the core DNA (different mitochondria) ( Vajta and Gjerris, 2005 ). Hence, the cloning of animals, primarily livestock animals, is a relatively new phenomenon.

2.2. Somatic Cell Nuclear Transfer (SCNT) technique

Over the last 20 years, Somatic Cell Nuclear Transfer (SCNT) has become indispensable in stem cell research with considerable potential in producing SCNT cloned animals. This technique is widely used to produce cells and tissues that are immune-compatible to the somatic cell donor ( Matoba and Zhang, 2018 ). SCNT appeared as brand-new biotechnology through which the possibilities derived from the advancements in molecular genetics and genome analysis in animal breeding. So far, more than 20 mammalian species have been cloned since the success of the first cloned mammal, Dolly the Sheep ( Matoba and Zhang, 2018 ).

The SCNT technique entails three essential steps: oocyte enucleation, implanting donor cells (or nucleus); and the reconstructed embryo ( Vajta and Gjerris, 2005 , Niemann, 2016 ). The cloned embryos are cultured in-vitro for some time, and once at their optimal level, the embryos are then transferred into the ‘parent’ animal ( Isa, 2013 ). In cloning, the nuclear genome (DNA) of a cell is replaced with another. The process is commenced by removing the maternal DNA from the mature oocyte, which is then replaced by the donor cell DNA ( UNESCO, 2005 ). Somatic cells may be derived from the animal, from cells grown through culture media or frozen tissues ( Committee on Science, Engineering and public policy, national academy of sciences, national academy of engineering, Institute of Medicine, 2002 ). A combination of chemicals is then introduced to prompt fertilisation, which results in the blastocyst stage. The derived embryo is then transferred or implanted into the uterus of an animal, followed by the natural process of pregnancy and birth ( Isa, 2013 ).

Animals bred through natural sexual reproduction contrasts from cloned animals that are a by-product of a combination of two random genes ( UNESCO, 2005 ). There are two possibilities. Firstly, if the ovum used is from the nucleus donor’s mother, or the nucleus of the donor itself ( Ayala, 2015 ). The resulting clone will hold the same genes (from the same nucleus and mitochondria) of the mother. The second possibility is if the ovum and nucleus used are from two distinct animals, or animals with different mothers. The resulting clone will then have a different gene as the genes are from differing mitochondria ( Ibtisham et al., 2016 ).

The success rate of animal cloning carried out by scientists, is still mostly inconsistent, with results profoundly dependent on the species and the type of cells used in the process. SCNT performance is relatively low, with success rates of 0.3–1.7 per cent per reconstructed oocyte and 3.4–13 per cent per transferred SCNT embryo ( Burgstaller and Brem, 2017 ). While complete nuclear transfer has been successfully cloned numerous mammals and has improved cloning performance, the proportion of cloned embryos that grow to full term remains poor, limiting the application of nuclear transfer technology ( Czernik et al., 2019 ). Furthermore, the cloned foetus miscarriage commonly occurs with a significant increase in the risk of foetus abnormality or mortality. Even after birth, developmental abnormalities remain in cloned mammals ( Loi et al., 2016 ).

The abnormalities and malformations resulted in the poor performance of SCNT that can be termed as the Large Offspring Syndrome (LOS), where the most commonly noted anomaly include the mismatch of size (cloned animals are too large for normal birth), as well as placental growth abnormalities ( Harris, 1997 , Ibtisham et al., 2017 ). LOS is now generally used in the discussion of other malformation and diseases. Besides the already existing complications, the unexpected mitochondrial dysfunctions in cloned embryos complicate the cloning process. Thus, it reduces the success rate ( Czernik et al., 2017 ). Several initiatives have, therefore, been implemented to boost the effectiveness of SCNT. These improvements include the technological aspects and the targeted alteration of the donor nucleus before or after the embryo’s development ( Czernik et al., 2016 ).

3. The application of animal cloning in agriculture

The recent advances in cloning efficiency have enabled diverse applications of SCNT technology. The advancement of SCNT in agriculture enhances the propagation of breeding farm animals and preserve the genetic resources of commercially important species, including cows and sheep ( Gomez et al., 2009 , Keefer, 2015 ). The weight of SCNT in the agricultural sector is more significant than in biomedicine. While the scientific and technological challenges of SCNT in both sectors are similar, employment in agriculture is more productive due to environmental variability and economic factors, such as cost efficiency, unique to agriculture. Cloning can be used to produce animals with desirable traits to yield healthier milk and meat for human consumption ( Paterson et al., 2003 ). The study administered by Takahashi & Yoshihio (2004) compares a sample of meat from cloned embryos, somatic clones and naturally produced animals, indicated no significant biological differences amongst the sample.

Genetically modified clones are considered more desirable than its traditionally bred counterpart, as clones tend to possess improved qualities such as healthier milk, meat and disease-resistant properties, resulting in a flow-on effect to benefit the wider population ( Vajta and Gjerris, 2005 ). One of the limitations of cloning in agriculture is its inability to produce consistent breeding animals’ results with the aspired traits ( Isa, 2013 ). It can be explained by the absence of a consistent mitochondrial DNA, as mitochondrial DNA varies according to the donor eggs. Also, the primary explanation for the low cloning competence is assumed to be the inability to reprogram the donor genome ( Rodriguez-Osorio et al., 2012 ). Further studies to enhance animal cloning efficiency such as bovine are needed to optimise the SCNT stage with an augmented recognition of the reprogramming mechanism ( Akagi et al., 2014 ). Moreover, the implementation of this technology depends not only on the animal’s genetic merits but also on the public perception and widespread acceptance of said technology ( Vajta and Gjerris, 2005 ).

4. Risk of the animal product derived from a cloned animal

The safety and ethical concerns associated with the products derived from modern biotechnology, especially cloned animals, are still controversial subjects ( Hasim et al., 2020 ). Nevertheless, previous studies have shown that animal products’ chemical composition, including meat and milk, is similar between clone-derived and nonclone-derived animals ( Hur, 2017 ). Most animal studies published that consuming meat and milk from cloned animals did not cause health problems and did not produce toxic effects. Dietary meat and milk derived from cloned animals also caused no adverse health effects such as reproduction and allergic reactions in animal models. Therefore, cloned animal meat and milk are as safe as food from their noncloned counterparts and can be consumed as novel foods ( Hur, 2017 ).

5. Islamic perspective on animal cloning

With the evolution of animal cloning in agriculture, naturally, the discussion of consuming foods from cloned animals is prompted. As a by-product of modern biotechnology processes, food is a comparatively brand-new concept, which requires new rulings that are more in line with the current developments. Before determining whether it is permissible or forbidden – haram or halal – to be consumed, this food category needs to be critically examined. Through the guidance of al-Qur’an and al-Sunnah (traditions of Prophet Muhammad PBUH), Muslims have relied on clear guidelines to determine the legality of matters. The general parameter on which the permissibility of a matter is based on is that unless something has been proven haram, or possessing haram features, Islam perceives the matter to be halal and permissible. The fiqh (Islamic jurisprudence) states:

الأصل في الأشياء الإباحة حتى يدل الدليل علي التحريم

“The original (basic) law for everything is permitted, unless there is an indication that shows the forbidden state of it.” ( al-Suyuti, 2001 , Nujaym, 1985 ).

Generally, Islam bans matters that are detrimental to one’s self. Thus, according to Islamic jurisprudence, the rulings for food as a by-product of modern biotechnology processes such as animal cloning should be determined based on the effects of its consumption by humans and whether it breaches any shariah principles. Following this belief, Muhammad Sulaiman al-Ashqar (2006) established the importance of Islamic organisations in examining the effects of food and medicinal products to provide a clearer understanding that can determine the permissibility of said food. Besides, the muftis are also accountable for researching animal-based food products, especially those produced through modern cloning methods ( Arifin, 2019 ). Hence, the Islamic authority needs to engage in extensive reviews regarding modern biotechnological processes, including animal cloning, to decide its permissibility in an Islamic context.

5.1. The determination of the permissibility of food derived from cloned animals

The permissibility of food’s analysis in this study is limited to the subject of food as a by-product of the modern biotechnological process of animal cloning. It is because cloning is generally performed as a means of breeding, for human consumption. It is vital to ensure that all new animal-based products produced through modern biotechnology must comply with the Quran and Sunnah requirements. ( Kashim et al., 2020 ). The views of the fuqaha’ regarding the permissibility of food derived from animals suggest that six principles could be used as a guideline in concluding the rulings of cloned animal-derived food. The principles are:

Principle one: Halal and haram animals

A modern food product produced from halal animals is deemed halal ( Husni et al., 2015 , Kashim et al., 2018a , Kashim et al., 2018b ). Following this principle, any food produced through biotechnological processes to cater to the modern Islamic community should first assess the permissibility (halal or haram) of the types of animals that form the basis or foundation of the developed food product ( Husni et al., 2012 ). It is fundamental to ensure that the benefits of food products produced through modern biotechnology application could be preserved ( Al-Bakri, 2019 ).

Principle two: Islamic process of animal slaughtering

There are essential conflicts of opinion between the Fuqaha’ in regards to the concept of al-dhakah . It happens due to the distinct understanding of the dalil for the process of slaughtering found in the Quran, the Sunnah, or through the practices of the Sahabahs ( al-Tariqi, 1983 , Rahman et al., 2018a , Rahman et al., 2018b ). The process of slaughtering requires the rupture of three critical veins: halqum (trachea); mariy’ (oesophagus) ; and wadajay (jugular). Therefore, cloned animals should benefit the Islamic community in every aspect and be slaughtered according to these principles ( Kashim et al., 2017 ).

Principle three: Not derived from a source of najis (impurity)

Cleanliness is one of Islam’s most critical aspects. Hence, it should also be considered in producing food derived from cloned animals ( Rahman et al., 2018a , Rahman et al., 2018b ). According to the Islamic Shariah, there are various sources of Najis (impurity), such as carcasses that were not slaughtered or animals that were cloned from an animal that is classified as Najis . For a cloned animal-derived food product to be defined as clean, and not a Najis , it should adhere strictly to the conditions as set out in the Islamic law, and not be contaminated with any sources of Najis , including flowing blood ( al-masfuh ) ( Kashim et al., 2015 ). According to Malaysian Standard (2019) , in MS1500:2019 document, najis is defined as matters that are impure according to Shariah law and fatwa ( Kashim et al., 2017 ).

Adherence to Islamic law should be emphasised as many studies attended on animal cloning that does not comply with Islamic law. For instance, transgenic paddy production requires cloning pig DNA in paddy plants that aim to develop paddy plants resistance to herbicides, which could increase rice production ( Kawahigashi et al., 2005 ). Additionally, there is also cloning of rat genes in potato trees for the same purpose ( Yamada et al., 2002 ). These animal cloning products are contrary to Islamic rules because there has been a mixing of haram and halal sources. On that basis, Malaysia’s mufti has banned such cloning to protect Muslims’ rights (Federal Territory Mufti, 2020).

Blood is often used in food processing. There are two contrasting forms of blood, the flowing and non-flowing blood. Both hold different laws. The four Madhab jurists have banned its use in all food products for the flowing blood, including GMOs. While non-flowing blood such as the liver, spleen, blood attached to animal flesh is halal eaten by Muslims (al-Nawawi t.th; al-Zuhayli 1998). Therefore, non-flowing blood in the processing of animal cloning products is considered halal following Islamic law (Federal Territory Mufti, 2020). Based on the fatwa, cloning-based food products from animal sources should be determined on a case-by-case basis. Consequently, in the legal issue of a clone-based product’s impurity, it needs to be decided based on the origin of the material taken.

Principle four: Istihalah tammah (perfect substance change)

The concept of Istihalah closely relates to aspects of cleanliness and purity ( taharah ), especially in the discussion of the modern biotechnological process of animal cloning. The Prophet Muhammad PBUH characterised cleanliness as one of the sources of Iman (faithfulness) of a Muslim (Qazzafiy, 2008). Istihalah tammah in animal cloning derived food is essential due to its purpose to purify impurities from contaminated substances. This process removes impurities from the originating body after it has been transferred into the new body.

The process of Istihalah , to purify Najis -contaminated substances, can either take place naturally or through human intervention. Substances’ status that was previously deemed haram could be changed to become halal and, in turn, be optimally used in various industries. For instance, the consumption or use of wine in food is haram. Nevertheless, through the process of istihalah , the wine can be fermented and turned into vinegar, which is halal to be consumed and used in food. Vinegar is considered halal, in contrast to its haram original form (wine), as the characteristics associated with wine, such as its smell, taste, and colour can no longer be identified. In line with this concept, food derived from the modern biotechnological process of animal cloning may be categorised as halal, given that it undergoes the process of istihalah tammah ( Kashim et al., 2019 ).

Principle five: Maslahah (public interest) and mafsadah (damage)

The Islamic jurisprudence ( fiqh ) scholars have defined the maslahah concept (public interest) as a method to confirm the permissibility of a matter based on serving the interest of the Muslim community – whether it is useful or poses harm ( al-Ghazali, M.M., 1992 , Abd and al-Salam, 2000 ). Al-Shatibi (1997) described maslahah as a process to ensure the continuity and livelihood of the human life, while other Islamic jurisprudence scholars defined maslahah as a necessity allowed by the shariah, to preserve one’s faith, soul, intellect, family and wealth ( Kashim et al., 2019 ).

The Ulama’ (Islamic scholars) agreed that in assessing the maslahah (public interest), and ultimately the permissibility of a matter, the interests to be served must satisfy the requirements of the Shariah (Islamic law). The maslahah (public interest) concept as a basis of law, must consider the five most influential factors that need to be preserved: religion, life, intellect, family and wealth ( al-Shatibi, 1997 ).

Mafsadah (damage), on the other hand, is a notion that is contrary to maslahah and is defined as something that causes harm in society, and which has been denied by Islamic law, due to its unfavourable impressions on religion, life, intellect, family and wealth ( Ibn Ashur, 2007 ).

Islam places high importance on the maslahah (public interest) of its followers in all aspects of life, including the effects of food produced through the modern biotechnological process of animal cloning ( Isa, 2013 ). The guideline in determining the permissibility of a matter in the context of Islamic law is commonly following the Islamic jurisprudence objectives of benefiting humankind and preventing harm from them. In the context of food, Allah has ordained upon Muslims to consume healthy, beneficial food while avoiding the contaminated and unhealthy food ( Kashim et al., 2020 ). However, in studying the maslahah of a matter, the benefits or the public interest should always adhere to the conditions set out in Shariah (Islamic law), to prevent the abuse of the concept of maslahah .

Based on researchers’ discussion on the maslahat and mafsadah, contemporary scholars have approved all types of animal cloning processes that lead to maslahat, such as medicines’ production to preserve human life (Maqasid al-Syariah). Islam also supports cloning in the agricultural sector if it can positively impact a country’s economy and as long as it does not abuse the transgenic animals (Federal Territory Mufti, 2020).

Nevertheless, contemporary scholars have banned all types of cloning processes that cause mafsadah, which induce harm to humans and animals ( Arifin, 2019 ). Islamic scholars in human cloning domain have declared an absolute ban. It is because human cloning does not meet the needs of maslahat but instead leads to greater mafsadah. For instance, ideas and studies on human cloning have insulted human glory created only by Almighty God. It worsens when cloning against humans will endanger lives and found various criminal offences in the future. Thus, prevention is better than cure ( Kashim et al., 2020 ).

f) Principle six: Darurat (exigency) of animal cloning

Darurat (exigency) refers to a situation that necessitates immediate action, and at which people often act irrationally and perform prohibited acts to protect their religion, soul, mind, family and wealth (al-Suyuti, n.d.). The fuqaha (scholars) have agreed that any prohibited acts done to preserve the abovementioned five maqasid , during an exigent period is exempted and is considered halal (permissible) ( al-Ramli, 1987 , Ibn et al., 1979 ). Nonetheless, to prevent the random and liberal use of this exclusion, the determination of a Darurat (exigent) situation should be in accordance to the conditions set out in Shariah (Islamic law) (Muhammad Adham, 2001; Rahman et al., 2019 ).

6. Conclusion

Animal cloning is a comparably new phenomenon which has amassed critical attention and research by scientists. The evolution of this technology renders imperative benefits, particularly in the biomedicine and agriculture sectors. In biomedicine, the advancement of SCNT could develop animal models to study the pathogenesis of human diseases and established genetically engineered xenograft organs for patient transplantation. Still, as much as numerous benefits it offers, animal cloning is exposed to some risks, including deformation and abnormalities related to the Large Offspring Syndrome (LOS). In addition to scientific concerns, animal cloning’s biotechnological process also exhibits some ethical issues such as ‘playing God’ and the technology’s abuse to clone other humans. From an Islamic viewpoint, the rulings of animal cloning’s permissibility could vary according to current circumstances and fatwas . The permissibility of animal cloning in Islam’s context depends essentially on its impacts on the Muslim community’s interests ( maslahah ) and whether there is an exigent need ( Darurat ) for said process.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgement

We thank the research project grant code FRGS/1/2019/SSI03/UKM/02/1 and FRGS/1/2017/SSI12/UKM/01/1 by Ministry of Higher Education, Malaysia for the supports.

Peer review under responsibility of King Saud University.

• Ibn Abd al-Salam, Abu Muhammad, A.A.A., 2000. al-Qawa’id al-Kubra, al-Mausu’ah bi Qawa’id al-Ahkam fi Islah al-Anam. Dimashq: Dar al-Qalam. Jil. 1.
• Akagi S., Matsukawa K., Takahashi S. Factors affecting the development of somatic cell nuclear transfer embryos in Cattle. J. Reprod. Dev. 2014;60(5):329–335. doi: 10.1262/jrd.2014-057. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Al-Bakri Z.M. Irsyad al-Fatwa. Penentuan hukum teknologi haiwan moden menurut Islam. Malaysia: Jabatan Mufti Wilayah Persekutuan. 2019 [ Google Scholar ]
• al-Ghazali, M.M., 1992. al-Mustashfa fi Ilmi al-Usul. al-Qaherah: Dar al-Haramayn.
• al-Ramli, M.I.A.A., 1987. Nihayat al-Muhtaj ila Sharh al-Minhaj fi al-Fiqh ‘ala Madhhab al-Imam al-Shafi’i. Beirut: Dar al-Gharb al-Islami.
• al-Shatibi, I.M., 1997. al-Muwafaqat fi Usul al-Shari’ah (Vol. 2). Beirut: Muassasat al-Risalah.
• al-Suyuti, A.A.A.B., 2001. al-Ashbah wa al-Nazair fi Madhhab al-Shafie (Vol. 1). Beirut: Dar al-Kutb al-Ilmiyyah.
• al-Tariqi, A.M., 1983. Ahkam al-Dhaba’ih wa al-Luhum al-Mustawradah fi al-Shari’ah al-Islamiyyah. Beirut: Muassasah al-Risalah.
• Amin L., Jamaluddin M.J., Abdul Rahim M.N., Osman Mohamad, Nor Muhammad M. Factors affecting public attitude toward genetically modified food in Malaysia. Sains Malaysiana. 2009;35(1):55. [ Google Scholar ]
• Arifin, L., 2019. Berita Harian. Sains, teknologi bantu penelitian hokum isu semasa. Malaysia: Kuala Lumpur.
• Ibn Ashur, Muhammad Tahir, 2007. Maqasid Shariah al-Islamiyyah. al-Qaherah: Dar al Salam.
• Ayala F.J. Cloning human? Biological, ethical, and social considerations. PNAS. 2015;12(29):8879–8886. doi: 10.1073/pnas.1501798112. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Benagiano G., Primiero F.M. Human reproductive cloning. Int. J. Gynecol. Obstet. 2002;79:265–268. doi: 10.1016/s0020-7292(02)00306-5. [ DOI ] [ PubMed ] [ Google Scholar ]
• Burgstaller, J.P., Brem, G., 2017. Aging of cloned animals: a mini-review. Gerontology; 63:417-425. doi: 10.1159/000452444 [ DOI ] [ PubMed ]
• Committee on science, engineering and public policy, national academy of sciences, national academy of engineering, institute of medicine. 2002. Retrieved from https://www.nap.edu/initiative/committee-on-science-engineering-and-public-policy
• Czernik M., Iuso D., Toschi P., Khochbin S., Loi P. Remodeling somatic nuclei via exogenous expression of protamine 1 to create spermatid-like structures for somatic nuclear transfer. Nat. Protoc. 2016;11(11):2170–2188. doi: 10.1038/nprot.2016.130. Epub 2016 Oct 6. [ DOI ] [ PubMed ] [ Google Scholar ]
• Czernik M., Toschi P., Zacchini F., Iuso D., Ptak G.E. Deregulated expression of mitochondrial proteins Mfn2 and Bcnl3L in placentae from sheep somatic cell nuclear transfer (SCNT) conceptuses. PLoS ONE. 2017;12(1) doi: 10.1371/journal.pone.0169579. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Czernik M., Anzalone D.A., Palazzese L., Oikawa M., Loi P. Somatic cell nuclear transfer: failures, successes and the challenges ahead. Int. J. Dev. Biol. 2019;63(3–4-5):123–130 doi: 10.1387/ijdb.180324mc. [ DOI ] [ PubMed ] [ Google Scholar ]
• FDA, 2008. Animal Cloning: A Risk Assessment. Rockville, MD, USA: Center for Veterinary Medicine, US Food and Drug Administration.
• Fiester A. Ethical issues in animal cloning. Perspect. Biol. Med. 2005;48(2):328–343. doi: 10.1353/pbm.2005.0072. [ DOI ] [ PubMed ] [ Google Scholar ]
• Gomez M.C., Pope C.E., Ricks D.M., Lyons J., Dumas C., Dresser B.L. Cloning endangered felids using heterospecific donor oocytes and interspecies embryo transfer. Reprod. Fertil. Dev. 2009;21:76–82. doi: 10.1071/rd08222. [ DOI ] [ PubMed ] [ Google Scholar ]
• Harris J. “Goodbye Dolly” The ethics of human cloning. J. Med. Ethics. 1997;23:353–360. doi: 10.1136/jme.23.6.353. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Hasim N.A., Kashim M.I.A.M., Othman R., Yahaya M.Z., Khalid R., Samsudin M.A. Haid daripada Perspektif Sains dan Maqasid Syariah. Sains Malaysiana. 2016;45(12):1879–1885. [ Google Scholar ]
• Hasim N.A., Amin L., Mahadi Z. Mohamed, Yusof N.A., Che Ngah A., Yaacob M., Olesen A.P.O., Abdul Aziz A. The integration and harmonisation of secular and Islamic ethical principles in formulating acceptable ethical principles in formulating acceptable ethical guidelines for modern biotechnology in Malaysia. Sci. Eng. Ethics. 2020;26:1797–1825. doi: 10.1007/s11948-020-00214-4. [ DOI ] [ PubMed ] [ Google Scholar ]
• Hur S.J. A study on current risk assessments and guidelines on the use of food animal products derived from cloned animals. Food Chem. Toxicol. 2017;108(Pt A):85–92. doi: 10.1016/j.fct.2017.07.047. [ DOI ] [ PubMed ] [ Google Scholar ]
• Husni A.M., Nor A.H.M., El-Seoudi A.W.M.M., Ibrahim I.A., Laluddin H., Samsudin M.A., Omar A.F., Alias M.N. Relationship of maqasid al-shariah with qisas and diyah: Analytical view. The Social Sci. 2012;7(5):725–730. [ Google Scholar ]
• Husni A.M., Nasohah Z., Kashim M.I.A.M. Problem of domestic violence and its solutions in the light of maqasid shariah. Asian Social Sci. 2015;11(22):33–42. [ Google Scholar ]
• Ibn Qudamah, Abd Allah ibn Ahmad. 1979. al-Mughbi fi Fiqh Imam al-Sunnah Ahmad ibn Hanba (Vol. 9). Beirut: Dar al-Fikr.
• Ibtisham F., Yanfeng N., Wang Z. Animal cloning drawbacks an-overview. J. Dairy Vet. Anim. Res. 2016;3(4):3–7. [ Google Scholar ]
• Ibtisham F., Fahd Qadir M.M., Xiao M., An L. Animal cloning applications and issues. Russian J. Genetics. 2017;53(9):965–971. [ Google Scholar ]
• Isa N. Universiti Malaya; Tesis PhD: 2013. Etika Dalam Bioteknologi Moden: Kajian ke atas Respons Para Ilmuwan Islam Terpilih Mengenai Garis Panduan Etika Islam. [ Google Scholar ]
• Kashim M.I.A.M., Majid L.A., Adnan A.H.M., Husni A.M., Nasohah Z., Samsudin M.A., Yahaya M.Z. Principles regarding the use of haram (forbidden) sources in food processing: A critical Islamic analysis. Asian Social Sci. 2015;11(22):17–25. [ Google Scholar ]
• Kashim M.I.A.M., Hasim N.A., Othaman R., Yahaya M.Z., Khalid R., Samsudin M.A., Zin D.M.M. Plasma darah dalam makanan dari perspektif Islam dan sains. Sains Malaysiana. 2017;46(10):1779–1797. [ Google Scholar ]
• Kashim M.I.A.M., Alias M.N., Zin D.M.M., Said N.L.M., Zakaria Z., Salleh A.D., Jamsari E.A. Istihalah and its effects on food: An Islamic perspective. Int. J. Civil Eng. Technol. 2018;9(1):755–762. [ Google Scholar ]
• Kashim M.I.A.M., Hasim N.A., Othaman R., Khalid R., Samsudin M.A., Yahaya M.Z., Abdul Manaf Z., Amin L., Mat Zin D.M. Najis (Tinja) manusia daripada perspektif sains dan Islam serta amalan pemakanan sunnah. Sains Malaysiana. 2018;47(6):1227–1234. [ Google Scholar ]
• Kashim M.I.A.M., Mohamad M.N., Sukor A.S.A., Adnan N.I.M., Safiai M.H., Jamsari E.Z. Animal urine therapy according to Islamic and scientific perspectives. Int. J. Civil Eng. Technol. 2019;10(02):2280–2286. [ Google Scholar ]
• Kashim M.I.A.M., Ab Rahman Z., Mohd Noor A.Y., Md Sham F., Hasim N.A., Safiai M.H., Mokhtar M.H., Hamjah S.H. Principles regarding the use of haram sources in modern food products: An Islamic perspective. J. Crit. Rev. 2020;7(6):1017–1024. [ Google Scholar ]
• Kawahigashi H., Hirose S., Ozawa K., Ido Y., Kojima M., Ohkawa H., Ohkawa Y. Analysis of substrate specificity of pig CYP2B22 and CYP2C49 towards herbicides by transgenic rice plants. Transgenic Res. 2005;14(6):907–917. doi: 10.1007/s11248-005-0199-x. [ DOI ] [ PubMed ] [ Google Scholar ]
• Keefer C.L. Artificial cloning of domestic animals. Proc. Natl. Acad. Sci. U.S.A. 2015;112:8874–8878. doi: 10.1073/pnas.1501718112. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Larijani B., Zahedi F. Islamic perspective on human cloning and stem cell research. Transpl. Proc. 2004;36:3188–3189. doi: 10.1016/j.transproceed.2004.10.076. [ DOI ] [ PubMed ] [ Google Scholar ]
• Loi P., Iuso D., Czernik M., Ogura A. A new dynamic Era for somatic cell nuclear transfer? Trends Biotechnol. 2016;34:791–797. doi: 10.1016/j.tibtech.2016.03.008. [ DOI ] [ PubMed ] [ Google Scholar ]
• Malaysian Standard, 2019. MS1500: 2019 Halal Food-General Requirements (Third Revision). Department of Malaysia Standard: Malaysia
• Matoba, S., Zhang, Y., 2018. Somatic Cell Nuclear Transfer Reprogramming: Mechanisms and Applications. Cell Stem Cell. 4;23(4):471-485. doi: 10.1016/j.stem.2018.06.018. Epub 2018 Jul 19. PMID: 30033121; PMCID: PMC6173619. [ DOI ] [ PMC free article ] [ PubMed ]
• McCreath K. Production of gene-targeted sheep by nuclear transfer from cultured somatic cells. Nature. 2000;40:1066–1069. doi: 10.1038/35016604. [ DOI ] [ PubMed ] [ Google Scholar ]
• Muhammad Sulaiman al-Ashqar . Dar al-Nafa’is; Beirut: 2006. Abhath Ijtihadiyyah fi al-Fiqh al-Tibb. [ Google Scholar ]
• Niemann H. Epigenetic reprogramming in mammalian species after SCNT-based cloning. Theriogenology. 2016;86(1):80–90. doi: 10.1016/j.theriogenology.2016.04.021. [ DOI ] [ PubMed ] [ Google Scholar ]
• Ibn Nujaym, Zayn al-Abidin, 1985. al-Ashbah wa al-Naza’ir ala Madhhab Abi Hanifah al-Nu’man (Vol. 1). Beirut: Dar al-Kutb al-Ilmiyyah.
• Paterson L., Desousa P., Ritchie W., King T., Wilmut I. Application of reproductive biotechnology in animals implications and potentials. Applications of reproductive cloning. Anim. Reprod. Sci. 2003;79:137–143. doi: 10.1016/s0378-4320(03)00161-1. [ DOI ] [ PubMed ] [ Google Scholar ]
• Phillips, K., 2002. Disease-resistant bull cloned at Texas A&M. Retrieved from: http://www.tamu.edu/aggiedaily/press/020214cc.html.
• Rahman Z.A., Ismail A., Abdullah S.N.H.S., Fauzi W.F., Suradi N.R.M. Developing self-identity among teens towards personal empowerment. Int. J. Civil Eng. Technol. 2018;9(13):674–684. [ Google Scholar ]
• Rahman Z.A., Noor A.Y.M., Abdullah S.N.H.S., Shaari A.H., Sarnon N. The relationship of Islamic cognitive reasoning elements and Islamic psychosocial as pillars in the self-empowerment of risky teenagers. Int. J. Civil Eng. Technol. 2018;9(8):1140–1150. [ Google Scholar ]
• Rahman Z.A., Ahmad Y.M.N., Yusof M.B., Mohamed S.B., Kashim M.I.A.M. Influence of prayers coping in problematic behaviors. Int. J. Civil Eng. Technol. 2019;10(2):826–835. [ Google Scholar ]
• Rodriguez-Osorio N., Urrego R., Cibelli J.B., Eilertsen K., Memili E. Reprogramming mammalian somatic cells. Theriogenology. 2012;78(9):1869–1886. doi: 10.1016/j.theriogenology.2012.05.030. [ DOI ] [ PubMed ] [ Google Scholar ]
• Samsudin M.A., Yahaya M.Z., Kashim M.I.A.M., Hayatullah L., Ahmad Munawar I., Rozida M.K., Irwan M.S., Syed Azhar S.S. Establishment of Shari’ah supervisory committee in Hospital: An analysis from perspective of public interest. Asian Social Sci. 2015;11(4):43–47. [ Google Scholar ]
• Takahashi S., Yoshihio I. Evaluation of meat products from cloned cattle: biological and biochemical properties. Cloning Stem Cells. 2004;6:165–171. doi: 10.1089/1536230041372265. [ DOI ] [ PubMed ] [ Google Scholar ]
• Thomas, T., 2003. Cloned and genetically engineered animals. Humane Society of the United States. Retrieved from: http://www.hsus.org/ace/15401
• UNESCO, 2005. Universal Declaration on Bioethics and Human Rights. [ PubMed ]
• Vajta G., Gjerris M. Science and technology of farm animal cloning: start of the art. Animal Reprod. Sci. 2005;92(3):211–230. doi: 10.1016/j.anireprosci.2005.12.001. [ DOI ] [ PubMed ] [ Google Scholar ]
• Yamada T., Ohashi Y., Ohshima M., Inui H., Shiota N., Ohkawa H., Ohkawa Y. Inducible cross-tolerance to herbicides in transgenic potato plants with the rat CYP1A1 gene. Theor. Appl. Genet. 2002;104(2–3):308–314. doi: 10.1007/s001220100736. [ DOI ] [ PubMed ] [ Google Scholar ]
• Zin D.D.M., Mohamed S., Kashim M.I.A.M., Jamsari E.Z., Kamaruzaman A.F., Rahman Z. Teachers’ knowledge and practice in implementing the thematic approach in pre-school. Int. J. Civil Eng. Technol. 2019;10(01):1870–1881. [ Google Scholar ]
• View on publisher site
• PDF (386.4 KB)
• Collections

Similar articles

Cited by other articles, links to ncbi databases.

• Download .nbib .nbib
• Format: AMA APA MLA NLM

Add to Collections

An official website of the United States government

The .gov means it's official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings
• Browse Titles

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

National Academy of Sciences (US), National Academy of Engineering (US), Institute of Medicine (US) and National Research Council (US) Committee on Science, Engineering, and Public Policy. Scientific and Medical Aspects of Human Reproductive Cloning. Washington (DC): National Academies Press (US); 2002.

Scientific and Medical Aspects of Human Reproductive Cloning.

• Hardcopy Version at National Academies Press

2 Cloning: Definitions And Applications

In this chapter, we address the following questions in our task statement:

What does cloning of animals including humans mean? What are its purposes? How does it differ from stem cell research?

To organize its response to those questions, the panel developed a series of subquestions, which appear as the section headings in the following text.

• WHAT IS MEANT BY REPRODUCTIVE CLONING OF ANIMALS INCLUDING HUMANS?

Reproductive cloning is defined as the deliberate production of genetically identical individuals. Each newly produced individual is a clone of the original. Monozygotic (identical) twins are natural clones. Clones contain identical sets of genetic material in the nucleus—the compartment that contains the chromosomes—of every cell in their bodies. Thus, cells from two clones have the same DNA and the same genes in their nuclei.

All cells, including eggs, also contain some DNA in the energy-generating “factories” called mitochondria. These structures are in the cytoplasm, the region of a cell outside the nucleus. Mitochondria contain their own DNA and reproduce independently. True clones have identical DNA in both the nuclei and mitochondria, although the term clones is also used to refer to individuals that have identical nuclear DNA but different mitochondrial DNA.

• HOW IS REPRODUCTIVE CLONING DONE?

Two methods are used to make live-born mammalian clones. Both require implantation of an embryo in a uterus and then a normal period of gestation and birth. However, reproductive human or animal cloning is not defined by the method used to derive the genetically identical embryos suitable for implantation. Techniques not yet developed or described here would nonetheless constitute cloning if they resulted in genetically identical individuals of which at least one were an embryo destined for implantation and birth.

The two methods used for reproductive cloning thus far are as follows:

• Cloning using somatic cell nuclear transfer ( SCNT ) [ 1 ]. This procedure starts with the removal of the chromosomes from an egg to create an enucleated egg. The chromosomes are replaced with a nucleus taken from a somatic (body) cell of the individual or embryo to be cloned. This cell could be obtained directly from the individual, from cells grown in culture, or from frozen tissue. The egg is then stimulated, and in some cases it starts to divide. If that happens, a series of sequential cell divisions leads to the formation of a blastocyst, or preimplantation embryo. The blastocyst is then transferred to the uterus of an animal. The successful implantation of the blastocyst in a uterus can result in its further development, culminating sometimes in the birth of an animal. This animal will be a clone of the individual that was the donor of the nucleus. Its nuclear DNA has been inherited from only one genetic parent.

The number of times that a given individual can be cloned is limited theoretically only by the number of eggs that can be obtained to accept the somatic cell nuclei and the number of females available to receive developing embryos. If the egg used in this procedure is derived from the same individual that donates the transferred somatic nucleus, the result will be an embryo that receives all its genetic material—nuclear and mitochondrial—from a single individual. That will also be true if the egg comes from the nucleus donor's mother, because mitochondria are inherited maternally. Multiple clones might also be produced by transferring identical nuclei to eggs from a single donor. If the somatic cell nucleus and the egg come from different individuals, they will not be identical to the nuclear donor because the clones will have somewhat different mitochondrial genes [ 2 ; 3 ]

• Cloning by embryo splitting. This procedure begins with in vitro fertilization ( IVF ): the union outside the woman's body of a sperm and an egg to generate a zygote. The zygote (from here onwards also called an embryo) divides into two and then four identical cells. At this stage, the cells can be separated and allowed to develop into separate but identical blastocysts, which can then be implanted in a uterus. The limited developmental potential of the cells means that the procedure cannot be repeated, so embryo splitting can yield only two identical mice and probably no more than four identical humans.

The DNA in embryo splitting is contributed by germ cells from two individuals—the mother who contributed the egg and the father who contributed the sperm. Thus, the embryos, like those formed naturally or by standard IVF , have two parents. Their mitochondrial DNA is identical. Because this method of cloning is identical with the natural formation of monozygotic twins and, in rare cases, even quadruplets, it is not discussed in detail in this report.

• WILL CLONES LOOK AND BEHAVE EXACTLY THE SAME?

Even if clones are genetically identical with one another, they will not be identical in physical or behavioral characteristics, because DNA is not the only determinant of these characteristics. A pair of clones will experience different environments and nutritional inputs while in the uterus, and they would be expected to be subject to different inputs from their parents, society, and life experience as they grow up. If clones derived from identical nuclear donors and identical mitocondrial donors are born at different times, as is the case when an adult is the donor of the somatic cell nucleus, the environmental and nutritional differences would be expected to be more pronounced than for monozygotic (identical) twins. And even monozygotic twins are not fully identical genetically or epigenetically because mutations, stochastic developmental variations, and varied imprinting effects (parent-specific chemical marks on the DNA) make different contributions to each twin [ 3 ; 4 ].

Additional differences may occur in clones that do not have identical mitochondria. Such clones arise if one individual contributes the nucleus and another the egg—or if nuclei from a single individual are transferred to eggs from multiple donors. The differences might be expected to show up in parts of the body that have high demands for energy—such as muscle, heart, eye, and brain—or in body systems that use mitochondrial control over cell death to determine cell numbers [ 5 ; 6 ].

• WHAT ARE THE PURPOSES OF REPRODUCTIVE CLONING?

Cloning of livestock [ 1 ] is a means of replicating an existing favorable combination of traits, such as efficient growth and high milk production, without the genetic “lottery” and mixing that occur in sexual reproduction. It allows an animal with a particular genetic modification, such as the ability to produce a pharmaceutical in milk, to be replicated more rapidly than does natural mating [ 7 ; 8 ]. Moreover, a genetic modification can be made more easily in cultured cells than in an intact animal, and the modified cell nucleus can be transferred to an enucleated egg to make a clone of the required type. Mammals used in scientific experiments, such as mice, are cloned as part of research aimed at increasing our understanding of fundamental biological mechanisms.

In principle, those people who might wish to produce children through human reproductive cloning [ 9 ] include:

• Infertile couples who wish to have a child that is genetically identical with one of them, or with another nucleus donor
• Other individuals who wish to have a child that is genetically identical with them, or with another nucleus donor
• Parents who have lost a child and wish to have another, genetically identical child
• People who need a transplant (for example, of cord blood) to treat their own or their child's disease and who therefore wish to collect genetically identical tissue from a cloned fetus or newborn.

Possible reasons for undertaking human reproductive cloning have been analyzed according to their degree of justification. For example, in reference 10 it is proposed that human reproductive cloning aimed at establishing a genetic link to a gametically infertile parent would be more justifiable than an attempt by a sexually fertile person aimed at choosing a specific genome.

Transplantable tissue may be available without the need for the birth of a child produced by cloning. For example, embryos produced by in vitro fertilization ( IVF ) can be typed for transplant suitability, and in the future stem cells produced by nuclear transplantation may allow the production of transplantable tissue.

The alternatives open to infertile individuals are discussed in Chapter 4 .

• HOW DOES REPRODUCTIVE CLONING DIFFER FROM STEM CELL RESEARCH?

The recent and current work on stem cells that is briefly summarized below and discussed more fully in a recent report from the National Academies entitled Stem Cells and the Future of Regenerative Medicine [ 11 ] is not directly related to human reproductive cloning. However, the use of a common initial step—called either nuclear transplantation or somatic cell nuclear transfer ( SCNT )—has led Congress to consider bills that ban not only human reproductive cloning but also certain areas of stem cell research. Stem cells are cells that have the ability to divide repeatedly and give rise to both specialized cells and more stem cells. Some, such as some blood and brain stem cells, can be derived directly from adults [ 12 - 19 ] and others can be obtained from preimplantation embryos. Stem cells derived from embryos are called embryonic stem cells ( ES cells ). The above-mentioned report from the National Academies provides a detailed account of the current state of stem cell research [ 11 ].

ES cells are also called pluripotent stem cells because their progeny include all cell types that can be found in a postimplantation embryo, a fetus, and a fully developed organism. They are derived from the inner cell mass of early embryos (blastocysts) [ 20 - 23 ]. The cells in the inner cell mass of a given blastocyst are genetically identical, and each blastocyst yields only a single ES cell line. Stem cells are rarer [ 24 ] and more difficult to find in adults than in preimplantation embryos, and it has proved harder to grow some kinds of adult stem cells into cell lines after isolation [ 25 ; 26 ].

Production of different cells and tissues from ES cells or other stem cells is a subject of current research [ 11 ; 27 - 31 ]. Production of whole organs other than bone marrow (to be used in bone marrow transplantation) from such cells has not yet been achieved, and its eventual success is uncertain.

Current interest in stem cells arises from their potential for the therapeutic transplantation of particular healthy cells, tissues, and organs into people suffering from a variety of diseases and debilitating disorders. Research with adult stem cells indicates that they may be useful for such purposes, including for tissues other than those from which the cells were derived [ 12 ; 14 ; 17 ; 18 ; 25 - 27 ; 32 - 43 ]. On the basis of current knowledge, it appears unlikely that adults will prove to be a sufficient source of stem cells for all kinds of tissues [ 11 ; 44 - 47 ]. ES cell lines are of potential interest for transplantation because one cell line can multiply indefinitely and can generate not just one type of specialized cell, but many different types of specialized cells (brain, muscle, and so on) that might be needed for transplants [ 20 ; 28 ; 45 ; 48 ; 49 ]. However, much more research will be needed before the magnitude of the therapeutic potential of either adult stem cells or ES cells will be well understood.

One of the most important questions concerning the therapeutic potential of stem cells is whether the cells, tissues, and perhaps organs derived from them can be transplanted with minimal risk of transplant rejection. Ideally, adult stem cells advantageous for transplantation might be derived from patients themselves. Such cells, or tissues derived from them, would be genetically identical with the patient's own and not be rejected by the immune system. However, as previously described, the availability of sufficient adult stem cells and their potential to give rise to a full range of cell and tissue types are uncertain. Moreover, in the case of a disorder that has a genetic origin, a patient's own adult stem cells would carry the same defect and would have to be grown and genetically modified before they could be used for therapeutic transplantation.

The application of somatic cell nuclear transfer or nuclear transplantation offers an alternative route to obtaining stem cells that could be used for transplantation therapies with a minimal risk of transplant rejection. This procedure—sometimes called therapeutic cloning, research cloning, or nonreproductive cloning, and referred to here as nuclear transplantation to produce stem cells —would be used to generate pluripotent ES cells that are genetically identical with the cells of a transplant recipient [ 50 ]. Thus, like adult stem cells, such ES cells should ameliorate the rejection seen with unmatched transplants.

Two types of adult stem cells—stem cells in the blood forming bone marrow and skin stem cells—are the only two stem cell therapies currently in use. But, as noted in the National Academies' report entitled Stem Cells and the Future of Regenerative Medicine , many questions remain before the potential of other adult stem cells can be accurately assessed [ 11 ]. Few studies on adult stem cells have sufficiently defined the stem cell's potential by starting from a single, isolated cell, or defined the necessary cellular environment for correct differentiation or the factors controlling the efficiency with which the cells repopulate an organ. There is a need to show that the cells derived from introduced adult stem cells are contributing directly to tissue function, and to improve the ability to maintain adult stem cells in culture without the cells differentiating. Finally, most of the studies that have garnered so much attention have used mouse rather than human adult stem cells.

ES cells are not without their own potential problems as a source of cells for transplantation. The growth of human ES cells in culture requires a “feeder” layer of mouse cells that may contain viruses, and when allowed to differentiate the ES cells can form a mixture of cell types at once. Human ES cells can form benign tumors when introduced into mice [ 20 ], although this potential seems to disappear if the cells are allowed to differentiate before introduction into a recipient [ 51 ]. Studies with mouse ES cells have shown promise for treating diabetes [ 30 ], Parkinson's disease [ 52 ], and spinal cord injury [ 53 ].

The ES cells made with nuclear transplantation would have the advantage over adult stem cells of being able to provide virtually all cell types and of being able to be maintained in culture for long periods of time. Current knowledge is, however, uncertain, and research on both adult stem cells and stem cells made with nuclear transplantation is required to understand their therapeutic potentials. (This point is stated clearly in Finding and Recommendation 2 of Stem Cells and the Future of Regenerative Medicine [ 11 ] which states, in part, that “studies of both embryonic and adult human stem cells will be required to most efficiently advance the scientific and therapeutic potential of regenerative medicine.”) It is likely that the ES cells will initially be used to generate single cell types for transplantation, such as nerve cells or muscle cells. In the future, because of their ability to give rise to many cell types, they might be used to generate tissues and, theoretically, complex organs for transplantation. But this will require the perfection of techniques for directing their specialization into each of the component cell types and then the assembly of these cells in the correct proportion and spatial organization for an organ. That might be reasonably straightforward for a simple structure, such as a pancreatic islet that produces insulin, but it is more challenging for tissues as complex as that from lung, kidney, or liver [ 54 ; 55 ].

The experimental procedures required to produce stem cells through nuclear transplantation would consist of the transfer of a somatic cell nucleus from a patient into an enucleated egg, the in vitro culture of the embryo to the blastocyst stage, and the derivation of a pluripotent ES cell line from the inner cell mass of this blastocyst. Such stem cell lines would then be used to derive specialized cells (and, if possible, tissues and organs) in laboratory culture for therapeutic transplantation. Such a procedure, if successful, can avoid a major cause of transplant rejection. However, there are several possible drawbacks to this proposal. Experiments with animal models suggest that the presence of divergent mitochondrial proteins in cells may create “minor” transplantation antigens [ 56 ; 57 ] that can cause rejection [ 58 - 63 ]; this would not be a problem if the egg were donated by the mother of the transplant recipient or the recipient herself. For some autoimmune diseases, transplantation of cells cloned from the patient's own cells may be inappropriate, in that these cells can be targets for the ongoing destructive process. And, as with the use of adult stem cells, in the case of a disorder that has a genetic origin, ES cells derived by nuclear transplantation from the patient's own cells would carry the same defect and would have to be grown and genetically modified before they could be used for therapeutic transplantation. Using another source of stem cells is more likely to be feasible (although immunosuppression would be required) than the challenging task of correcting the one or more genes that are involved in the disease in adult stem cells or in a nuclear transplantation-derived stem cell line initiated with a nucleus from the patient.

In addition to nuclear transplantation, there are two other methods by which researchers might be able to derive ES cells with reduced likeli hood for rejection. A bank of ES cell lines covering many possible genetic makeups is one possibility, although the National Academies report entitled Stem Cells and the Future of Regenerative Medicine rated this as “difficult to conceive” [ 11 ]. Alternatively, embryonic stem cells might be engineered to eliminate or introduce certain cell-surface proteins, thus making the cells invisible to the recipient's immune system. As with the proposed use of many types of adult stem cells in transplantation, neither of these approaches carries anything close to a promise of success at the moment.

The preparation of embryonic stem cells by nuclear transplantation differs from reproductive cloning in that nothing is implanted in a uterus. The issue of whether ES cells alone can give rise to a complete embryo can easily be misinterpreted. The titles of some reports suggest that mouse embryos can be derived from ES cells alone [ 64 - 72 ]. In all cases, however, the ES cells need to be surrounded by cells derived from a host embryo, in particular trophoblast and primitive endoderm. In addition to forming part of the placenta, trophoblast cells of the blastocyst provide essential patterning cues or signals to the embryo that are required to determine the orientation of its future head and rump (anterior-posterior) axis. This positional information is not genetically determined but is acquired by the trophoblast cells from events initiated soon after fertilization or egg activation. Moreover, it is critical that the positional cues be imparted to the inner cells of the blastocyst during a specific time window of development [ 73 - 76 ]. Isolated inner cell masses of mouse blastocysts do not implant by themselves, but will do so if combined with trophoblast vesicles from another embryo [ 77 ]. By contrast, isolated clumps of mouse ES cells introduced into trophoblast vesicles never give rise to anything remotely resembling a postimplantation embryo, as opposed to a disorganized mass of trophoblast. In other words, the only way to get mouse ES cells to participate in normal development is to provide them with host embryonic cells, even if these cells do not remain viable throughout gestation (Richard Gardner, personal communication). It has been reported that human [ 20 ] and primate [ 78 - 79 ] ES cells can give rise to trophoblast cells in culture. However, these trophoblast cells would presumably lack the positional cues normally acquired during the development of a blastocyst from an egg. In the light of the experimental results with mouse ES cells described above, it is very unlikely that clumps of human ES cells placed in a uterus would implant and develop into a fetus. It has been reported that clumps of human ES cells in culture, like clumps of mouse ES cells, give rise to disorganized aggregates known as embryoid bodies [ 80 ].

Besides their uses for therapeutic transplantation, ES cells obtained by nuclear transplantation could be used in laboratories for several types of studies that are important for clinical medicine and for fundamental research in human developmental biology. Such studies could not be carried out with mouse or monkey ES cells and are not likely to be feasible with ES cells prepared from normally fertilized blastocysts. For example, ES cells derived from humans with genetic diseases could be prepared through nuclear transplantation and would permit analysis of the role of the mutated genes in both cell and tissue development and in adult cells difficult to study otherwise, such as nerve cells of the brain. This work has the disadvantage that it would require the use of donor eggs. But for the study of many cell types there may be no alternative to the use of ES cells; for these cell types the derivation of primary cell lines from human tissues is not yet possible.

If the differentiation of ES cells into specialized cell types can be understood and controlled, the use of nuclear transplantation to obtain genetically defined human ES cell lines would allow the generation of genetically diverse cell lines that are not readily obtainable from embryos that have been frozen or that are in excess of clinical need in IVF clinics. The latter do not reflect the diversity of the general population and are skewed toward genomes from couples in which the female is older than the period of maximal fertility or one partner is infertile. In addition, it might be important to produce stem cells by nuclear transplantation from individuals who have diseases associated with both simple [81] and complex (multiple-gene) heritable genetic predilections. For example, some people have mutations that predispose them to “Lou Gehrig's disease” (amyotrophic lateral sclerosis, or ALS); however, only some of these individuals become ill, presumably because of the influence of additional genes. Many common genetic predilections to diseases have similarly complex etiologies; it is likely that more such diseases will become apparent as the information generated by the Human Genome Project is applied. It would be possible, by using ES cells prepared with nuclear transplantation from patients and healthy people, to compare the development of such cells and to study the fundamental processes that modulate predilections to diseases.

Neither the work with ES cells , nor the work leading to the formation of cells and tissues for transplantation, involves the placement of blastocysts in a uterus. Thus, there is no embryonic development beyond the 64 to 200 cell stage, and no fetal development.

2-1. Reproductive cloning involves the creation of individuals that contain identical sets of nuclear genetic material ( DNA ). To have complete genetic identity, clones must have not only the same nuclear genes, but also the same mitochondrial genes.

2-2. Cloned mammalian animals can be made by replacing the chromosomes of an egg cell with a nucleus from the individual to be cloned, followed by stimulation of cell division and implantation of the resulting embryo.

2-3. Cloned individuals, whether born at the same or different times, will not be physically or behaviorally identical with each other at comparable ages.

2-4. Stem cells are cells that have an extensive ability to self-renew and differentiate, and they are therefore important as a potential source of cells for therapeutic transplantation. Embryonic stem cells derived through nuclear transplantation into eggs are a potential source of pluripotent (embryonic) stem cell lines that are immunologically similar to a patient's cells. Research with such cells has the goal of producing cells and tissues for therapeutic transplantation with minimal chance of rejection.

2-5. Embryonic stem cells and cell lines derived through nuclear transplantation could be valuable for uses other than organ transplantation. Such cell lines could be used to study the heritable genetic components associated with predilections to a variety of complex genetic diseases and test therapies for such diseases when they affect cells that are hard to study in isolation in adults.

2-6. The process of obtaining embryonic stem cells through nuclear transplantation does not involve the placement of an embryo in a uterus, and it cannot produce a new individual.

• Cite this Page National Academy of Sciences (US), National Academy of Engineering (US), Institute of Medicine (US) and National Research Council (US) Committee on Science, Engineering, and Public Policy. Scientific and Medical Aspects of Human Reproductive Cloning. Washington (DC): National Academies Press (US); 2002. 2, Cloning: Definitions And Applications.
• PDF version of this title (5.5M)
• Disable Glossary Links

In this Page

Related information.

• PMC PubMed Central citations
• PubMed Links to PubMed

Recent Activity

• Cloning: Definitions And Applications - Scientific and Medical Aspects of Human ... Cloning: Definitions And Applications - Scientific and Medical Aspects of Human Reproductive Cloning

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Connect with NLM

National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894

Web Policies FOIA HHS Vulnerability Disclosure

Help Accessibility Careers