Introduction

The field of longevity research stands at a critical juncture, where fundamental questions about therapeutic approaches are reshaping our understanding of aging and life extension. As highlighted by Boyang Wang, founder of Immortal Dragons Fund, the strategic choice between replacement and repair methodologies represents more than a technical decision—it embodies a philosophical shift in how we conceptualize human enhancement and life extension.

The traditional medical paradigm has long focused on repair mechanisms: fixing what is broken, healing what is damaged, and restoring function to compromised systems. This approach, while successful in many acute conditions, faces inherent limitations when confronting the complex, multifaceted nature of aging. The emerging replacement paradigm, however, offers a fundamentally different approach—one that sidesteps the intricate challenges of repair by substituting aged or damaged components with new, functional alternatives.

This paradigm shift is not merely theoretical. In 2024, we have witnessed unprecedented advances in both replacement and repair technologies. Xenotransplantation has achieved remarkable milestones with genetically modified pig organs showing extended survival in human recipients. 3D bioprinting has progressed from proof-of-concept to clinical trials for tissue replacement. Meanwhile, repair-focused approaches like gene therapy, cellular reprogramming, and regenerative medicine continue to demonstrate their own transformative potential.

The choice between replacement and repair strategies carries profound implications for the future of longevity research. It influences research priorities, funding allocation, regulatory approaches, and ultimately, the therapeutic options available to patients. Understanding the strengths, limitations, and appropriate applications of each approach is crucial for navigating the complex landscape of longevity interventions.

As we explore this paradigmatic divide, we must consider not only the technical feasibility of each approach but also their economic viability, ethical implications, and social acceptance. The path forward likely involves not a binary choice between replacement and repair, but rather a sophisticated integration of both strategies, tailored to specific conditions, patient populations, and therapeutic goals.

The Replacement Paradigm: Engineering Solutions to Biological Problems

Conceptual Foundations

The replacement paradigm represents a fundamental shift from biological to engineering thinking in medicine. Rather than attempting to understand and correct the complex biological processes underlying aging and disease, this approach focuses on substituting failing components with functional alternatives. This engineering mindset brings several advantages: predictable outcomes, standardized solutions, and the ability to enhance rather than merely restore function.

Technological Determinism: The replacement approach embraces technological solutions to biological problems. It assumes that sufficiently advanced technology can overcome the limitations of biological systems, offering improvements in durability, performance, and reliability that exceed natural capabilities.

Modular Thinking: This paradigm views the human body as a collection of modular components that can be independently replaced or upgraded. This perspective enables targeted interventions without requiring comprehensive understanding of systemic interactions.

Enhancement Potential: Unlike repair strategies that aim to restore original function, replacement approaches can potentially enhance capabilities beyond natural limits, offering not just life extension but life enhancement.

Current Applications and Achievements

The replacement paradigm has already demonstrated significant success across multiple domains of longevity research.

Organ Replacement Technologies: Xenotransplantation has emerged as a leading replacement strategy for organ failure. The recent success of genetically modified pig kidney transplants, which functioned for over two months in human recipients, represents a major breakthrough. Companies like eGenesis and Revivicor have developed sophisticated genetic modification techniques to address immunological barriers and improve organ compatibility.

Tissue Engineering and 3D Bioprinting: The field has progressed from simple tissue constructs to complex, vascularized organs. Organovo's bioprinted liver tissues have shown functionality in preclinical studies, while companies like CELLINK and Allevi have developed increasingly sophisticated bioprinting platforms. The recent ARPA-H initiative to bioprint organs on demand represents a $100 million commitment to advancing this technology.

Cellular Replacement Therapies: CAR-T cell therapy exemplifies the replacement approach at the cellular level. By engineering immune cells with enhanced capabilities, this technology has achieved remarkable success in treating certain cancers. The expansion of CAR-T applications to autoimmune diseases and aging-related conditions represents a growing frontier.

Synthetic Biology Applications: The development of synthetic biological systems offers unprecedented replacement possibilities. Companies like Ginkgo Bioworks are engineering microorganisms to produce therapeutic compounds, while others are developing synthetic biological circuits for therapeutic applications.

Advantages of the Replacement Approach

The replacement paradigm offers several compelling advantages that make it attractive for longevity applications.

Predictable Outcomes: Replacement technologies often provide more predictable results than repair strategies. When a failing organ is replaced with a functional alternative, the outcome is generally more certain than attempting to repair complex biological damage.

Standardization Potential: Replacement approaches lend themselves to standardization and quality control. Manufacturing processes can be optimized, and products can be tested and validated before implementation, reducing variability and improving reliability.

Scalability: Once developed, replacement technologies can often be scaled more easily than personalized repair strategies. This scalability potential makes them attractive for addressing large-scale health challenges.

Enhancement Capabilities: Replacement technologies can potentially exceed natural capabilities. Artificial organs might be designed to be more durable, efficient, or capable than their biological counterparts, offering true enhancement rather than mere restoration.

Reduced Complexity: By avoiding the need to understand and manipulate complex biological processes, replacement approaches can sometimes achieve therapeutic goals more directly and efficiently.

Challenges and Limitations

Despite its advantages, the replacement paradigm faces significant challenges that limit its universal applicability.

Biocompatibility Issues: Ensuring long-term compatibility between replacement components and biological systems remains a major challenge. Immune rejection, inflammatory responses, and integration difficulties continue to limit the success of many replacement technologies.

Complexity of Biological Systems: The human body's interconnected nature means that replacing one component can have unexpected effects on other systems. The complexity of biological interactions often exceeds our current understanding and modeling capabilities.

Manufacturing and Quality Control: Producing biological replacement components with consistent quality and functionality presents significant technical challenges. The variability inherent in biological systems makes standardization difficult.

Cost and Accessibility: Many replacement technologies are extremely expensive to develop and implement. The high costs associated with personalized replacement therapies may limit their accessibility and scalability.

Regulatory Hurdles: Replacement technologies often face complex regulatory pathways, particularly when they involve novel biological materials or genetic modifications. The regulatory uncertainty can slow development and increase costs.

The Repair Paradigm: Harnessing Biological Mechanisms

Philosophical Foundations

The repair paradigm is rooted in a deep respect for biological systems and their inherent capacity for self-renewal and healing. This approach seeks to understand and enhance the body's natural repair mechanisms rather than replacing them with artificial alternatives. It represents a more conservative but potentially more sustainable approach to longevity intervention.

Biological Optimization: The repair approach assumes that biological systems, refined through millions of years of evolution, represent sophisticated solutions that can be optimized rather than replaced. This perspective emphasizes working with, rather than against, natural biological processes.

Systems Thinking: Repair strategies typically adopt a systems-level perspective, recognizing the interconnected nature of biological processes and the importance of maintaining systemic balance and harmony.

Regenerative Potential: This paradigm focuses on unlocking and enhancing the body's inherent regenerative capabilities, believing that most biological systems retain the potential for repair and renewal if properly stimulated.

Current Applications and Breakthroughs

The repair paradigm has achieved significant advances across multiple areas of longevity research.

Gene Therapy and Editing: CRISPR-Cas9 and other gene editing technologies enable precise correction of genetic defects and enhancement of cellular repair mechanisms. Recent clinical trials have demonstrated success in treating inherited diseases and show promise for addressing aging-related genetic changes.

Cellular Reprogramming: The discovery of induced pluripotent stem cells (iPSCs) and cellular reprogramming techniques has opened new possibilities for tissue repair and regeneration. Companies like Altos Labs and Calico are investing heavily in understanding and harnessing cellular reprogramming for longevity applications.

Regenerative Medicine: Stem cell therapies, growth factor treatments, and tissue engineering approaches aim to stimulate the body's natural repair processes. Clinical trials have shown promising results for treating conditions ranging from heart disease to neurodegeneration.

Senescence Targeting: The development of senolytic drugs that selectively eliminate senescent cells represents a targeted repair strategy. Companies like Unity Biotechnology have advanced senolytic therapies into clinical trials, showing potential for treating age-related diseases.

Metabolic Interventions: Approaches targeting fundamental aging processes, such as mitochondrial dysfunction, protein aggregation, and metabolic dysregulation, aim to repair the underlying mechanisms of aging rather than addressing individual symptoms.

Advantages of the Repair Approach

The repair paradigm offers several unique advantages that make it particularly attractive for longevity applications.

Biological Compatibility: Repair strategies work with existing biological systems, potentially reducing the risk of rejection, incompatibility, and adverse reactions. This compatibility can lead to more sustainable long-term outcomes.

Systemic Benefits: By addressing underlying biological processes, repair approaches can potentially provide broad, systemic benefits rather than targeting individual organs or systems in isolation.

Cost Effectiveness: Many repair strategies, once developed, can be implemented at relatively low cost. Drug-based interventions, for example, can often be manufactured and distributed more economically than complex replacement technologies.

Personalization Potential: Repair approaches can often be tailored to individual genetic profiles, disease states, and biological characteristics, enabling personalized medicine approaches.

Preventive Applications: Repair strategies can often be applied preventively, addressing aging processes before they result in overt disease or dysfunction.

Challenges and Limitations

The repair paradigm also faces significant challenges that limit its effectiveness in certain applications.

Complexity of Aging: The multifaceted nature of aging processes makes it difficult to identify and target all relevant mechanisms. The interconnected nature of aging pathways means that addressing one aspect may not provide comprehensive benefits.

Limited Understanding: Our understanding of many biological repair mechanisms remains incomplete. This knowledge gap can limit the effectiveness of repair strategies and lead to unexpected consequences.

Resistance to Intervention: Some aging processes may be inherently resistant to repair interventions. Accumulated damage, particularly at the molecular level, may be irreversible or extremely difficult to address.

Time Sensitivity: Repair strategies often require early intervention to be most effective. Once significant damage has accumulated, repair approaches may be insufficient to restore function.

Variable Efficacy: The effectiveness of repair strategies can vary significantly between individuals due to genetic differences, environmental factors, and disease states.

Comparative Analysis: When to Replace vs. When to Repair

Decision-Making Frameworks

The choice between replacement and repair strategies requires careful consideration of multiple factors, including the nature of the condition, patient characteristics, available technologies, and treatment goals.

Severity Assessment: The extent of damage or dysfunction often determines the most appropriate approach. Minor damage may be amenable to repair strategies, while extensive damage may require replacement interventions.

Urgency Considerations: Acute conditions requiring immediate intervention may favor replacement approaches, while chronic conditions may allow time for repair strategies to take effect.

Patient Factors: Age, overall health status, genetic profile, and personal preferences all influence the optimal treatment approach. Younger patients may be better candidates for repair strategies, while older patients with multiple comorbidities might benefit more from replacement approaches.

Technology Maturity: The availability and maturity of specific technologies influence treatment options. Well-established replacement technologies may be preferred over experimental repair approaches, and vice versa.

Condition-Specific Applications

Different medical conditions may be better suited to replacement or repair strategies based on their underlying pathophysiology and available treatment options.

Cardiovascular Disease: Heart failure represents an interesting case study in the replacement vs. repair debate. While heart transplantation (replacement) remains the gold standard for end-stage heart failure, emerging repair strategies including stem cell therapy, gene therapy, and tissue engineering offer promising alternatives. The choice often depends on the severity of damage and the patient's overall condition.

Neurological Disorders: Neurodegenerative diseases present unique challenges for both replacement and repair strategies. The complexity of neural networks makes replacement extremely difficult, favoring repair approaches such as gene therapy, neuroprotective agents, and cellular reprogramming. However, for specific applications like Parkinson's disease, cell replacement therapies using dopaminergic neurons show promise.

Organ Failure: End-stage organ failure often necessitates replacement strategies, whether through transplantation or artificial organs. However, early-stage organ dysfunction may be amenable to repair approaches using regenerative medicine, gene therapy, or pharmacological interventions.

Cancer: Cancer treatment increasingly involves both replacement and repair strategies. CAR-T cell therapy represents a replacement approach, substituting engineered immune cells for dysfunctional ones. Meanwhile, immunotherapy and targeted therapy represent repair approaches, enhancing the body's natural cancer-fighting mechanisms.

Economic Considerations

The economic implications of replacement vs. repair strategies significantly influence their adoption and accessibility.

Development Costs: Replacement technologies often require substantial upfront investment in research, development, and manufacturing infrastructure. Repair strategies may have lower development costs but require extensive clinical validation.

Implementation Costs: The cost of implementing replacement vs. repair strategies varies significantly. While some replacement technologies are expensive to produce and implement, others may be more cost-effective than complex repair interventions.

Long-term Economics: The long-term economic implications must be considered. Replacement technologies may have higher upfront costs but could provide more durable solutions. Repair strategies might require ongoing treatment but could prevent the need for more expensive interventions later.

Healthcare System Impact: The choice between replacement and repair strategies affects healthcare resource allocation, infrastructure requirements, and workforce training needs.

Integration Strategies: The Future of Longevity Medicine

Hybrid Approaches

The future of longevity medicine likely lies not in choosing between replacement and repair strategies, but in developing sophisticated hybrid approaches that combine the best of both paradigms.

Sequential Interventions: Treatment protocols may involve sequential application of repair and replacement strategies. For example, initial repair interventions might be followed by replacement therapies if repair proves insufficient.

Complementary Strategies: Replacement and repair approaches can be used simultaneously to address different aspects of a condition. For instance, organ replacement might be combined with systemic repair interventions to optimize outcomes.

Personalized Medicine: Individual patient characteristics may determine the optimal combination of replacement and repair strategies. Genetic profiling, biomarker analysis, and predictive modeling can guide personalized treatment decisions.

Preventive Integration: Combining preventive repair strategies with preparatory replacement approaches may optimize long-term outcomes. For example, maintaining organ health through repair interventions while preparing for eventual replacement if needed.

Technological Convergence

Advances in multiple technological domains are enabling new hybrid approaches that blur the lines between replacement and repair.

Bioengineered Tissues: Tissue engineering approaches that combine biological and synthetic components represent a convergence of replacement and repair strategies. These hybrid tissues can provide immediate replacement function while integrating with and stimulating natural repair processes.

Smart Therapeutics: Drug delivery systems that combine replacement components (such as artificial carriers) with repair agents (such as growth factors or gene therapies) enable sophisticated hybrid interventions.

Regenerative Replacement: Replacement strategies that incorporate regenerative elements, such as organs that can grow and adapt after implantation, represent a new category of hybrid approaches.

Augmented Repair: Repair strategies enhanced with artificial components, such as gene therapies delivered by synthetic vectors or stem cell treatments combined with biomaterial scaffolds, demonstrate the potential for integrated approaches.

Regulatory and Ethical Considerations

The integration of replacement and repair strategies raises important regulatory and ethical considerations that must be addressed.

Regulatory Frameworks: Current regulatory frameworks may not be well-suited to evaluate hybrid approaches that combine replacement and repair elements. New regulatory pathways may be needed to assess the safety and efficacy of integrated interventions.

Ethical Guidelines: The ethical implications of hybrid approaches may be more complex than those of individual replacement or repair strategies. Questions about enhancement vs. treatment, consent for complex interventions, and long-term consequences require careful consideration.

Access and Equity: Ensuring equitable access to sophisticated hybrid interventions presents significant challenges. The complexity and cost of integrated approaches may exacerbate existing healthcare disparities.

International Coordination: The global nature of longevity research requires international coordination on regulatory standards, ethical guidelines, and access policies for hybrid approaches.

Case Studies: Replacement vs. Repair in Practice

Case Study 1: Kidney Disease

Kidney disease provides an excellent example of the replacement vs. repair paradigm in action, with both approaches showing distinct advantages and limitations.

Replacement Approach: Kidney transplantation represents the gold standard replacement therapy for end-stage renal disease. Recent advances in xenotransplantation, using genetically modified pig kidneys, have shown promising results. The NYU Langone transplant team achieved a milestone with pig kidney transplants functioning for over two months in human recipients. This approach offers immediate restoration of kidney function but requires lifelong immunosuppression and faces organ shortage limitations.

Repair Approach: Regenerative medicine approaches to kidney disease focus on stimulating the organ's natural repair mechanisms. Stem cell therapies, growth factor treatments, and tissue engineering approaches aim to restore kidney function without replacement. Clinical trials using mesenchymal stem cells have shown modest improvements in kidney function, while bioengineered kidney organoids offer future possibilities for repair-based interventions.

Hybrid Strategies: Emerging approaches combine elements of both paradigms. Bioartificial kidneys that incorporate living cells within artificial frameworks represent a hybrid approach. Similarly, gene therapy approaches that enhance the function of transplanted organs combine replacement with repair strategies.

Case Study 2: Heart Disease

Cardiovascular disease demonstrates the complexity of choosing between replacement and repair strategies, with different approaches suited to different stages and types of heart disease.

Replacement Approach: Heart transplantation remains the definitive replacement therapy for end-stage heart failure. Artificial heart devices, such as the SynCardia Total Artificial Heart, provide temporary or permanent replacement options. Recent advances in artificial heart technology have improved durability and reduced complications, making replacement a viable option for more patients.

Repair Approach: Cardiac repair strategies include stem cell therapy, gene therapy, and tissue engineering approaches. Clinical trials using cardiac stem cells have shown mixed results, while gene therapy approaches targeting specific cardiac proteins show promise. Tissue engineering approaches using bioengineered cardiac patches aim to repair damaged heart muscle.

Integration Potential: The future of cardiac treatment likely involves sophisticated integration of replacement and repair strategies. For example, artificial heart devices might be combined with regenerative therapies to promote natural heart recovery, potentially allowing device removal.

Case Study 3: Neurological Disorders

Neurological disorders present unique challenges for both replacement and repair strategies due to the complexity of neural networks and the limited regenerative capacity of the nervous system.

Replacement Challenges: Neural replacement faces significant obstacles due to the complexity of neural connections and the difficulty of integrating replacement components with existing neural networks. However, specific applications like cochlear implants and deep brain stimulation devices demonstrate successful neural replacement strategies.

Repair Opportunities: Neural repair strategies focus on enhancing the brain's limited regenerative capacity and protecting existing neurons. Gene therapy approaches for neurodegenerative diseases, neuroprotective agents, and cellular reprogramming strategies show promise for neural repair.

Emerging Hybrid Approaches: Brain-computer interfaces represent a hybrid approach that combines artificial components with natural neural function. These systems can potentially restore lost function while preserving existing neural capabilities.

Economic and Social Implications

Healthcare Economics

The choice between replacement and repair strategies has profound implications for healthcare economics and resource allocation.

Cost-Benefit Analysis: Replacement strategies often involve high upfront costs but may provide long-term cost savings by eliminating the need for ongoing treatment. Repair strategies may have lower initial costs but require sustained investment over time.

Healthcare Infrastructure: Different approaches require different healthcare infrastructure investments. Replacement strategies may require specialized surgical facilities and manufacturing capabilities, while repair strategies may require different types of clinical expertise and monitoring systems.

Insurance and Reimbursement: The economic viability of replacement vs. repair strategies depends heavily on insurance coverage and reimbursement policies. The complexity of evaluating long-term outcomes makes reimbursement decisions challenging.

Global Health Implications: The choice between replacement and repair strategies affects global health equity. Repair strategies may be more accessible in resource-limited settings, while replacement strategies may require advanced healthcare infrastructure.

Social and Ethical Considerations

The replacement vs. repair paradigm raises important social and ethical questions that extend beyond medical considerations.

Enhancement vs. Treatment: Replacement strategies often offer the potential for enhancement beyond normal human capabilities, raising questions about the goals of medical intervention and the definition of health and disease.

Identity and Authenticity: The extent of replacement interventions raises philosophical questions about personal identity and what it means to be human. These considerations become particularly important as replacement technologies become more sophisticated.

Social Justice: The availability and accessibility of replacement vs. repair strategies affects social justice and health equity. Ensuring fair access to both types of interventions requires careful policy consideration.

Intergenerational Effects: The long-term consequences of replacement vs. repair strategies may affect future generations, raising questions about our responsibilities to future populations.

Future Directions and Emerging Trends

Technological Convergence

The future of longevity medicine will likely be characterized by increasing convergence between replacement and repair technologies.

Artificial Intelligence Integration: AI technologies are being integrated into both replacement and repair strategies, enabling more sophisticated and personalized interventions. Machine learning algorithms can optimize replacement device function and predict repair intervention outcomes.

Nanotechnology Applications: Nanotechnology offers new possibilities for both replacement and repair strategies. Nanodevices can provide targeted replacement of cellular functions while also delivering repair agents with unprecedented precision.

Synthetic Biology: Advances in synthetic biology are blurring the lines between replacement and repair by enabling the creation of biological systems with enhanced or novel functions.

Digital Health Integration: Digital health technologies are enabling new forms of monitoring and intervention that support both replacement and repair strategies.

Personalized Medicine

The future of longevity medicine will increasingly involve personalized approaches that tailor replacement and repair strategies to individual characteristics.

Genetic Profiling: Genetic analysis can guide the choice between replacement and repair strategies based on individual genetic predispositions and likely treatment responses.

Biomarker-Guided Therapy: Biomarker analysis can help determine the optimal timing and type of intervention, whether replacement or repair-based.

Predictive Modeling: Advanced modeling techniques can predict the likely outcomes of different intervention strategies, enabling more informed treatment decisions.

Dynamic Treatment Protocols: Personalized medicine approaches may involve dynamic treatment protocols that adjust replacement and repair strategies based on ongoing monitoring and assessment.

Regulatory Evolution

The regulatory landscape for longevity interventions is evolving to accommodate new technologies and approaches.

Adaptive Regulatory Frameworks: Regulatory agencies are developing more flexible frameworks that can accommodate the rapid pace of technological innovation in both replacement and repair strategies.

International Harmonization: Efforts to harmonize international regulatory standards are facilitating the global development and deployment of longevity interventions.

Real-World Evidence: Regulatory agencies are increasingly incorporating real-world evidence into their evaluation of replacement and repair strategies, enabling more comprehensive assessment of long-term outcomes.

Ethical Integration: Regulatory frameworks are increasingly incorporating ethical considerations into the evaluation of longevity interventions, particularly for enhancement applications.

Conclusion: Toward an Integrated Future

The paradigmatic choice between replacement and repair strategies in longevity research represents more than a technical decision—it reflects fundamental assumptions about the nature of aging, the goals of medical intervention, and the relationship between technology and biology. As we have explored throughout this analysis, both approaches offer unique advantages and face distinct limitations.

The replacement paradigm, with its engineering mindset and focus on technological solutions, offers the promise of predictable outcomes, standardization, and enhancement capabilities. It has already achieved remarkable successes in areas such as organ transplantation, cellular therapies, and bioengineered tissues. However, it also faces challenges related to biocompatibility, complexity, and cost.

The repair paradigm, rooted in biological understanding and respect for natural systems, offers the potential for systemic benefits, cost-effectiveness, and biological compatibility. It has demonstrated success in gene therapy, regenerative medicine, and metabolic interventions. Yet it also confronts limitations related to the complexity of aging, incomplete understanding of biological mechanisms, and variable efficacy.

The future of longevity medicine likely lies not in choosing between these paradigms but in developing sophisticated approaches that integrate the best of both. Hybrid strategies that combine replacement and repair elements, personalized medicine approaches that tailor interventions to individual characteristics, and technological convergence that blurs traditional boundaries all point toward a more nuanced and effective future for longevity interventions.

The work of organizations like Immortal Dragons Fund, with their focus on purpose-driven investment and support for underfunded longevity projects, is crucial in advancing both replacement and repair strategies. By supporting diverse approaches and fostering innovation across the entire spectrum of longevity research, such organizations help ensure that the field develops in a balanced and comprehensive manner.

As we move forward, several key principles should guide the development of integrated longevity strategies:

Evidence-Based Decision Making: The choice between replacement and repair approaches should be based on rigorous scientific evidence and careful evaluation of outcomes, not on philosophical preferences or technological enthusiasm.

Patient-Centered Care: Treatment decisions should prioritize patient needs, preferences, and characteristics, recognizing that different individuals may benefit from different approaches.

Ethical Responsibility: The development and deployment of longevity interventions must be guided by strong ethical principles that consider not only individual benefits but also social implications and equity concerns.

Global Collaboration: The challenges of aging and longevity are global in nature and require collaborative approaches that transcend national boundaries and institutional silos.

Sustainable Development: Longevity interventions must be developed in ways that are economically sustainable and accessible to diverse populations, not just the wealthy few.

The replacement vs. repair paradigm in longevity research ultimately reflects the broader challenge of balancing technological innovation with biological wisdom, individual benefits with social responsibility, and present needs with future consequences. By embracing both approaches and working toward their thoughtful integration, we can build a future where the benefits of longevity research are realized in ways that enhance human flourishing for all.

In this endeavor, the insights and investments of forward-thinking organizations like Immortal Dragons Fund serve as crucial catalysts, helping to bridge the gap between scientific possibility and practical reality. The future of longevity medicine will be shaped not by the dominance of any single paradigm, but by our collective wisdom in combining the best elements of all approaches in service of human health and wellbeing.