Abstract
Oral diseases such as dental caries (DC) and periodontitis are widely prevalent, and existing approaches to managing these conditions have only a limited effect. Accordingly, there is growing interest in the development of novel biological interventions (including, among others, CRISPR-Cas9) that might, in the future, be used to prevent the development of or cure these conditions. However, in addition to familiar concerns about using biological interventions in children who cannot provide valid consent, it is not clear whether the provision of these interventions would fall within the proper domain of dentistry. In this opinion paper, we defend the view that the provision of reasonably safe and effective novel biological interventions aimed at preventing DC and periodontitis should be understood to fall within the proper domain of dentistry. To do so, we first argue that their use would be consistent with existing practice in dentistry. We then argue that: i) they may substantially increase the recipient's wellbeing and future autonomy; and ii) that their use could constitute a form of indirect preventative medicine by addressing a threat to systemic health.
Key points
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Provides an update on new biotechnologies that will help oral health improvement.
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Explores a discussion about novel interventions in dentistry and the questions that could potentially arise for them to come into practice.
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Presents an argument in defence of dentistry to enhance human biology using novel bio-tools in development.
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Displays what dentists should start thinking about with regards to the impact of gene editing in clinical practice.
Introduction
Oral diseases such as dental caries (DC) and periodontitis are highly prevalent around the world.1,2,3,4 At the biological level, it is natural for DC, periodontitis and tooth loss (TL) to arise widely in our species,5,6,7 making it a statistical norm for the human species to live with these oral 'diseases'. Once established, these conditions are highly associated with systemic diseases and can ultimately lead to TL, which impacts social and psychological wellbeing.8,9,10,11
Conditions such as DC and periodontitis are complex to treat, and as yet no cure has been found for them. Instead, current treatments offered in day-to-day practice aimed at managing DC, periodontitis and its sequelae TL are either generally restorative or aim to halt disease progression. Furthermore, dentists will commonly recommend behavioural strategies (such as flossing and tooth brushing) that aim to prevent the onset of DC and periodontitis. Yet, as we shall explain below, all of these existing interventions have only limited effects.
Technological advances in dentistry are raising the prospect of new strategies for tackling these conditions. Indeed, it is likely that DC and periodontitis will be targets for novel capacity-altering, biologically based interventions that aim to tackle direct biological risk factors beyond individual fronts of oral disease. However, the prospect of these novel interventions raises moral questions about the proper domain of dentistry.
In this article, we shall argue that dentistry should seek the prevention and cure of DC and periodontitis using novel, biological, capacity-altering interventions, in view of considerations of wellbeing and consistency with accepted dental practices.
Existing approaches in dentistry and new frontiers
The destroyed dental and oral structures in DC and periodontitis result in burdens for life, requiring restoration and additional maintenance throughout one's lifetime. Such interventions aim to restore oral health functionality/hygiene, aiding life extension of the dental organ(s), not to cure. Therefore, seeking to prevent/generate immunity for common oral conditions is still of great importance for oral health.
Although behaviour change has been shown to be efficient in significantly decreasing the number of affected teeth over time,12,13 there are three key factors influencing the effectiveness of that approach: first, independently of socioeconomic status, the personal perceptions of a patient or patient's family on the importance of the behavioural change ultimately influences treatment adherence;14,15 second, manual dexterity;16 and third, genetic and epigenetic factors.17,18,19,20 Furthermore, some patients can develop DC and periodontitis even in an optimal (behaviour) oral hygiene regime scenario; for example, they may do so if they suffer from amelogenesis/dentinogenesis imperfecta,21 hereditary gingival fibromatosis, or experience periodontitis as a manifestation of systemic disease.22,23
Therefore, there is a need for novel interventions that prevent and/or cure DC and periodontitis at a more fundamental level, targeting the biological processes underlying these diseases. Gene-editing technologies such as CRISPR-Cas9 offer some promise in this regard.24,25,26 A reliable predictive genetic marker for DC or periodontitis does not currently exist, but many candidate genes have been proposed.17,18,19 Moreover, DC and periodontitis develop as a result of gene-environmental interaction,17,18,19,20,27,28 suggesting that gene editing offers a potential therapeutic avenue in dentistry, in addition to behavioural enhancement approaches. The use of CRISPR-Cas9 for dental conditions has not been widely discussed, in part because the technology is still in its infancy outside of dentistry, and its safety and efficacy has not yet been established for more serious life-threatening conditions. However, should the safety of the technique be established in the future, such an approach could offer a potential avenue for altering host regulatory genes that are an integral part of fighting against the infectious aspect of DC and periodontitis.29
Moreover, somatic gene-editing interventions could also potentially have important preventative effects. First, somatic interventions could be used to modulate the composition of the native oral microbiome,29 or the pathogenicity of the bacteria causative of DC and periodontitis. If successful, such an approach could decrease the damage caused to the dental organ and supportive tissues, preventing early disease stage development.30 Alternatively, gene editing could be used to modulate dental organ tissues and their supportive apparatus.31,32 Such tissues are constantly exposed to pathogens and commensal microorganisms. Therefore, the ability of local cell populations to respond to the environmental factors could be enhanced via gene editing.
Consistency with current practice
As we suggested above, dentists already attempt to prevent DC and periodontitis by advocating behavioural change. Oral hygiene habits have shown to be successful in TL decrease,12,13 even though such measures were initially met with scepticism in the mid-twentieth century.33
Of course, it may be argued that there is a difference between advocating behavioural changes and performing biologically based interventions. For instance, one might appeal to the fact that the latter infringes on a right to bodily integrity that the former does not. However, whether or not there is a morally significant disanalogy between advocating behavioural changes and performing biologically based interventions is something of a moot point, since dentistry has also already fought to universally implement and perform a biological intervention that is still widely used today - universal systemic water fluoridation. This intervention has been shown to be effective in reducing levels of tooth decay among children.34 Moreover, topical fluoride application to teeth in the dental practice and fissure sealants are also used to prevent DC.35 Whether it is via changing behaviour or through the use of biological interventions, we believe that it is (and always has been) within the professional and ethical domain of dentistry to pursue novel biological preventative and curative strategies against DC, periodontitis and TL.
Considerations for using capacity-altering, biologically based approaches in dentistry
Many of the biological interventions we consider would be either performed prenatally or before adulthood. This has significant implications for their potential moral permissibility, as the recipients cannot provide valid consent to the intervention. However, we often rely on parents to make proxy decisions for their children with regards to preventative medicine. For example, we already allow parents to exercise parental autonomy in order to prevent children developing dental disease by ensuring oral hygiene in their children. Notably, there are also some risks with providing children with oral hygiene; if parents are neglectful or lazy, they may risk causing fluoride-associated conditions in children, which in extreme levels can be toxic and fatal.36
The reason that parental autonomy appears justifiable here is that choosing to prevent oral disease in one's children, by ensuring oral hygiene, meets the following criteria of the kinds of biological interventions that parents may permissibly choose for their children. The intervention in question must be:
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1.
Safe
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2.
Unlikely to result in harm to others
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3.
Compatible with the demands of distributive justice
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4.
Such that the parent's choices are based on a plausible conception of wellbeing and a better life for the child
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5.
Consistent with development of autonomy in the child and a reasonable range of future life plans.37
As we have already mentioned, one of the main concerns about the use of gene editing in any context is safety.
In the context of dentistry, there is risk of disruption of neural crest commitment to craniofacial formation;38 therefore, there is a very long way to go before we have a safe and reliable gene-editing technique that would be morally permissible to use for even the most serious medical conditions. Accordingly, our discussion of the use of gene editing in dentistry is naturally oriented towards a future time where the safety and reliability of gene-editing techniques has reached a satisfactory level, such that they might be considered for preventing the harms associated with oral disease.
In the interests of brevity, we shall thus set aside issues raised by safety, as well as harm to others and distributive justice. However, we shall argue that novel biological interventions in dentistry could meet conditions 4 and 5.
Wellbeing and future autonomy
DC and periodontitis are detrimental to wellbeing. The greater the number of reported toothaches, decayed teeth, cases of periodontal disease and missing teeth, the poorer is a person's quality of life.9,39,40 Negative judgements are made about people with flawed dentition, affecting their everyday experiences41,42 and raising the chances for bullying in children.43 Safe and effective biological interventions that prevent or cure DC, periodontitis and TL would enhance the child's wellbeing on any plausible conception, and they would be consistent with the development of the child's future autonomy.
There is of course scope for debate about the level and type of wellbeing of which it is the professional responsibility of dentists to achieve. It might be argued that DC, periodontitis and TL are universal diseases, and so it does not fall within the domain of dentistry to cure (rather than simply treat) these conditions. However, this line of objection overlooks a significant body of research suggesting that these conditions also affect systemic health.44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61 Oral diseases are directly linked to systemic health and some life-threatening diseases. Therefore, capacity-altering interventions for prevention and cure of DC and periodontitis may not only result in common oral diseases benefits, but also in systemic health benefits.
Seeking to cure and prevent these conditions can thus be viewed as a form of indirect preventative medicine. As such, we should not assume that novel biological interventions aimed at securing these benefits will only be permissible if they pose no risk. Some low level of risk may be proportionate, although the precise level of risk to which it would be reasonable to expose children for the sake of these benefits is a question that we cannot adequately address here.
Conclusion
The real problem with existing preventive measures for oral diseases is their ineffectiveness, rather than the strategy of prevention per se. DC is still the most common non-communicable disease worldwide, consuming 5-10% of healthcare budgets in industrialised countries, and is among the main reasons for hospitalisation of children in some high-income countries.3 We suggest that DC and periodontitis cure and prevention by means of novel biological capacity-altering interventions is consistent with the historic and current pursuit of preventative measures already adopted in dentistry. Therefore, potential future use of novel biological capacity-altering interventions should fall within the moral domain of dentistry.
References
World Health Organisation. Oral health. Available at https://www.who.int/news-room/fact-sheets/detail/oral-health (accessed September 2020).
Peres M A, Macpherson L M D, Weyant R J et al. Oral diseases: a global public health challenge. Lancet 2019; 394: 249-260.
World Health Organisation. Sugars and dental caries. 2017. Available at https://www.who.int/news-room/fact-sheets/detail/sugars-and-dental-caries (accessed September 2020).
Kassebaum N J, Bernabé E, Dahiya M, Bhandari B, Murray C J, Marcenes W. Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression. J Dent Res 2014; 93: 1045-1053.
Boorse C. Health as a theoretical concept. Philos Sci 1977; 44: 542-573.
Oxilia G, Peresani M, Romandini M et al. Earliest evidence of dental caries manipulation in the Late Upper Palaeolithic. Sci Rep 2015; 5: 12150.
Löe H, Anerud A, Boysen H. The natural history of periodontal disease in man: prevalence, severity, and extent of gingival recession. J Periodontol 1992; 63: 489-495.
Exley C. Bridging a gap: the (lack of a) sociology of oral health and healthcare. Sociol Health Illn 2009; 31: 1093-1108.
Garcia R I, Henshaw M M, Krall E A. Relationship between periodontal disease and systemic health. Periodontol 2000 2001; 25: 21-36.
Hosseinpoor A R, Itani L, Petersen P E. Socio-economic inequality in oral healthcare coverage: results from the World Health Survey. J Dent Res 2012; 91: 275-281.
Asimakopoulou K G. The psychological effects of toothloss - a guide for clinicians. Aesthetic Dentistry Today. 2017.
Sälzer S, Alkilzy M, Slot D E et al. Socio-behavioural aspects in the prevention and control of dental caries and periodontal diseases at an individual and population level. J Clin Periodontol 2017; 44 Suppl 18: S106-S115.
Axelsson P, Nyström B, Lindhe J. The long-term effect of a plaque control programme on tooth mortality, caries and periodontal disease in adults. Results after 30 years of maintenance. J Clin Periodontol 2004; 31: 749-757.
Kelly M P, Barker M. Why is changing health-related behaviour so difficult? Public Health 2016; 136: 109-116.
Asimakopoulou K, Newton J T, Daly B, Kutzer Y, Ide M. The effects of providing periodontal disease risk information on psychological outcomes - a randomized controlled trial. J Clin Periodontol 2015; 42: 350-355.
Barouch K, Al Asaad N, Alhareky M. Clinical relevance of dexterity in oral hygiene. Br Dent J 2019; 226: 354-357.
American Dental Association. Genetics and oral health. Available at https://www.ada.org/en/member-centre/oral-health-topics/genetics-and-oral-health (accessed September 2020).
Nibali L, Di Iorio A, Tu Y K, Vieira A R. Host genetics role in the pathogenesis of periodontal disease and caries. J Clin Periodontol 2017; 44 Suppl 18: S52-S78.
Nibali L, Bayliss-Chapman J, Almofareh S A, Zhou Y, Divaris K, Vieira A R. What Is the Heritability of Periodontitis? A Systematic Review. J Dent Res 2019; 98: 632-641.
Benakanakere M R, Finoti L, Palioto D B, Teixeira H S, Kinane D F. Epigenetics, Inflammation, and Periodontal Disease. Curr Oral Health Rep 2019; 6: 37-46.
Witkop Jr C J. Amelogenesis imperfecta, dentinogenesis imperfecta and dentin dysplasia revisited: problems in classification. J Oral Pathol 1988; 17: 547-553.
Gawron K, Łazarz-Bartyzel K, Potempa J, Chomyszyn-Gajewska M. Gingival fibromatosis: clinical, molecular and therapeutic issues. Orphanet J Rare Dis 2016; 11: 9.
Watanabe K. Prepubertal periodontitis: a review of diagnostic criteria, pathogenesis, and differential diagnosis. J Periodontal Res 1990; 25: 31-48.
Anonymous. Method of the Year 2011. Nat Methods 2012; 9: 1.
Doudna J A, Charpentier E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 2014; 346: 1258096.
Cribbs A P, Perera S M W. Science and Bioethics of CRISPR-Cas9 Gene Editing: An Analysis Towards Separating Facts and Fiction. Yale J Biol Med 2017; 90: 625-634.
Marsh P D, Zaura E. Dental biofilm: ecological interactions in health and disease. J Clin Periodontol 2017; 44 Suppl 18: S12-S22.
Lamont R J, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol 2018; 16: 745-759.
Yu N, Yang J, Mishina Y, Giannobile W V. Genome Editing: A New Horizon for Oral and Craniofacial Research. J Dent Res 2019; 98: 36-45.
Zhou H, Zhao H, Zheng J et al. CRISPRs provide broad and robust protection to oral microbial flora of gingival health against bacteriophage challenge. Protein Cell 2015; 6: 541-545.
Gordon L M, Cohen M J, MacRenaris K W, Pasteris J D, Seda T, Joester D. Dental materials. Amorphous intergranular phases control the properties of rodent tooth enamel. Science 2015; 347: 746-750.
Benakanakere M R, Finoti L S, Tanaka U, Grant G R, Scarel-Caminaga R M, Kinane D F. Investigation of the functional role of human Interleukin-8 gene haplotypes by CRISPR/Cas9 mediated genome editing. Sci Rep 2016; 6: 31180.
Brauer J C, Demeritt W M, Higley L B, Lindahl R L, Massler M, Schour I. Dentistry for Children. New York: McGraw-Hill, 1958.
Iheozor-Ejiofor Z, Worthington H V, Walsh T et al. Water fluoridation for the prevention of dental caries. Cochrane Database Syst Rev 2015; DOI: 10.1002/14651858.CD010856.pub2.
Ahovuo-Saloranta A, Forss H, Hiiri A, Nordblad A, Mäkelä M. Pit and fissure sealants versus fluoride varnishes for preventing dental decay in the permanent teeth of children and adolescents. Cochrane Database Syst Rev 2016; DOI: 10.1002/14651858.CD003067.pub4.
World Health Organisation. International Programme on Chemical Safety: Fluorides. 2002. Available online at https://apps.who.int/iris/handle/10665/42415 (accessed September 2020).
Savulescu J. Genetic Interventions and The Ethics of Enhancement of Human Beings. In Steinbock B (ed) The Oxford Handbooks of Bioethics. Oxford: Oxford University Press, 2009.
Helms J A, Cordero D, Tapadia M D. New insights into craniofacial morphogenesis. Development 2005; 132: 851-861.
Kelly M, Steele J, Nuttall N et al. Adult dental health survey. Oral health in the United Kingdom. London: The Stationary Office, 2000.
Davis D M, Fiske J, Scott B, Radford D R. The emotional effects of tooth loss: a preliminary quantitative study. Br Dent J 2000; 188: 503-506.
Hendrie C A, Brewer G. Evidence to suggest that teeth act as human ornament displays signalling mate quality. PLoS One 2012; DOI: 10.1371/journal.pone.0042178.
Somani A, Newton J T, Dunne S, Gilbert D B. The impact of visible dental decay on social judgements: comparison of the effects of location and extent of lesion. Int Dent J 2010; 60: 169-174.
Al-Bitar Z B, Al-Omari I K, Sonbol H N, Al-Ahmad H T, Cunningham S J. Bullying among Jordanian schoolchildren, its effects on school performance, and the contribution of general physical and dentofacial features. Am J Orthod Dentofacial Orthop 2013; 144: 872-878.
Holmberg P, Hellmich T, Homme J. Paediatric Sepsis Secondary to an Occult Dental Abscess: A Case Report. J Emerg Med 2017; 52: 744-748.
Christensen L, Evans H, Cundick D, McShane M, Penna K, Sadoff R. Necrotizing Fasciltis Case Presentation and Literature Review. N Y State Dent J 2015; 81: 24-28.
McDonnough J A, Ladzekpo D A, Yi I, Bond Jr W R, Ortega G, Kalejaiye A O. Epidemiology and resource utilization of ludwig's angina ED visits in the United States 2006-2014. Laryngoscope 2019; 129: 2041-2044.
Pine C M, Harris R V, Burnside G, Merrett M C. An investigation of the relationship between untreated decayed teeth and dental sepsis in 5-year-old children. Br Dent J 2006; 200: 45-29.
Gilway D, Brown S J. Medical emergencies: Sepsis in primary dental care. Br Dent J 2016; 220: 278.
Mullin G. On death's door: Firefighter nearly dies after getting POPCORN stuck in his teeth - when it triggered deadly heart infection. The Sun (London) 2020 January 6.
Paraskevas S, Huizinga J D, Loos B G. A systematic review and meta-analyses on C-reactive protein in relation to periodontitis. J Clin Periodontol 2008; 35: 277-290.
Billings F. Chronic focal infections and their etiologic relations to arthritis and nephritis. Arch Intern Med 1912; 9: 484-498.
Tonetti M S, Van Dyke T E, Working group 1 of the joint EFP/AAP workshop. Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Clin Periodontol 2013; 40: S24-S29.
D'Aiuto F, Gkranias N, Bhowruth D et al. Systemic effects of periodontitis treatment in patients with type 2 diabetes: a 12 month, single-centre, investigator-masked, randomised trial. Lancet Diabetes Endocrinol 2018; 6: 954-965.
Ide M, Harris M, Stevens A et al. Periodontitis and Cognitive Decline in Alzheimer's Disease. PLoS One 2016; DOI: 10.1371/journal.pone.0151081.
Dominy S S, Lynch C, Ermini F et al. Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv 2019; DOI: 10.1126/sciadv.aau3333.
Sanz M, Marco Del Castillo A, Jepsen S et al. Periodontitis and cardiovascular diseases: Consensus report. J Clin Periodontol 2020; 47: 268-288.
Helenius-Hietala J, Suominen A L, Ruokonen H et al. Periodontitis is associated with incident chronic liver disease-A population-based cohort study. Liver Int 2019; 39: 583-591.
Ioannidou E, Swede H. Disparities in periodontitis prevalence among chronic kidney disease patients. J Dent Res 2011; 90: 730-734.
D'Aiuto F, Sabbah W, Netuveli G et al. Association of the metabolic syndrome with severe periodontitis in a large U S. population-based survey. J Clin Endocrinol Metab 2008; 93: 3989-3994.
Chapple I L, Genco R; working group 2 of the joint EFP/AAP workshop. Diabetes and periodontal diseases: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Periodontol 2013; 84(4 Suppl): S106-S112.
Baeza M, Morales A, Cisterna C et al. Effect of periodontal treatment in patients with periodontitis and diabetes: systematic review and meta-analysis. J Appl Oral Sci 2020; DOI: 10.1590/1678-7757-2019-0248.
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VN, JP and JS all contributed with ideas and to the drafting of the manuscript. All authors have agreed to the final version.
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VN currently receives funding from the Academy of Medical Sciences; JP currently receives funding from UKRI; JS currently receives funding from the Wellcome Trust (WT203132/Z/16/Z).
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Neves, V., Pugh, J. & Savulescu, J. Beyond oral hygiene, are capacity-altering, biologically based interventions within the moral domain of dentistry?. Br Dent J 231, 277–280 (2021). https://doi.org/10.1038/s41415-021-3335-y
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DOI: https://doi.org/10.1038/s41415-021-3335-y