Biosafety and Bioethical issues in Biotechnology BIOSAFETY Biosafety

Biosafety and Bioethical issues in Biotechnology

BIOSAFETY ‘Biosafety’ means the need to protect human and animal health and environment from the possible adverse effects of the products of modern biotechnology

How is Genetic Engineering (GE) different from conventional breeding (CB)? n n Combining DNA in new combinations and introducing it into a new organism are the GE tools. Main differences between CB and GE Ø Ability to move across sexual barriers Ø Amount of change: a specific gene embodying a particular trait or thousands of genes embodying desirable and undesirable traits Ø Occurrence of change in one or several generations.

Genetic engineering: Recombinant DNA technology

Is GE inherently unsafe? n n Two diametrically opposite trends of thought US-Canada n No new risks associated with GM crops n New regulations not considered necessary n Safety assessments Ø ‘Product’ rather than ‘process’ based Ø In comparison and contrast to their ‘familiarity’ and ‘substantial’ equivalence to conventional crops

…Is GE inherently unsafe? n EU n n n Safety assessment n n n GE crops considered new and special Existing legislation not considered sufficient Process based Principle of ‘substantial equivalence’ beginning rather than the end Adoption of ‘Precautionary Principle’ as guide

…. Is GE inherently unsafe? n n GE technology carries certain inherent unpredictability Some facts n Isolation of a gene from its natural environment and integration into entirely different organism n Possible transgenic instability due to triggering of the inbuilt defense mechanisms of the host organism leading to inactivation or silencing of foreign genes.

…. Is GE inherently unsafe? n Possibilities of integration of foreign gene at a site predisposed to silencing of genes (position effect). Ø Variance in the levels of expression of the transgene in different environmental conditions (heat, humidity, light…. . ) Ø Possibilities of silencing of genes arising in subsequent generations Case by case sound scientific assessment is of utmost significance

Biosafety issues in transgenic crops n n Relate to environmental, human and animal health consequences Both can have short and long term implications Biosafety risks involve the entire spectrum of biodiversity A universal ‘true for all’ approach may not be applicable Risks Known Probability Unknown Probability • Rigorous Scientific Assessment • Risk Mitigation • Precautionary Principle

. . Biosafety issues in transgenic crops Biosafety concerns arise from: n n n Horizontal gene transfer Genetic contamination Transfer of allergens and toxins from one life form to another and creation of new toxins and allergenic compounds

. . Biosafety issues in transgenic crops -Main Concerns Ø Development of aggressive weeds/ wild relatives by transfer of transgenic traits Ø Erosion of land races/wild relatives by genetic pollution in centres of origin/ diversity Ø Harm to the non-target organisms Ø Development of pest resistance by prolonged use Ø Monoculture and limitations to farmers’ choice in crop management Ø Hazard to human and animal health by transfer of toxins and allergens and by creation of new toxins and allergenic compounds

. . Biosafety issues in transgenic crops Assessment n n n GE venturing into an unknown biological territory ASILOMAR Conference (1975): No research till safety guidelines in place Initially, focus on laboratory safety procedures Wider definition of biosafety with possibilities of commercialization of GM products The broad format of biosafety parametres essentially the same in all regulations

. . Biosafety issues in transgenic crops Two main stages: 1. 2. Laboratory/green house stage Confined Trial Stage IMPORTANT Prevention of the spread of genetically engineered material outside lab/field

Laboratory/green house stage n. Different biosafety levels as per the degree of risk involved n. Two methods of containment v. Physical v. Biological

Confined Trial Stage A confined trial is a small scale release of a transgenic plant species for research purposes conducted under conditions that prevent spread of the organism and mitigate its impact on the surrounding environment Objective is to collect data to evaluate the crops’ performance

Focus on Risk Mitigation Risk mitigation – the terms and conditions that are necessary to conduct the trial safely. n n n Prevent Gene Flow Prevent entry of GMOs into food chain Prevent Persistence of GMOs in the field

Bio-pharmaceutical therapeutics Biosafety risk n Survival, multiplication and dissemination of GMOs in contained/ open environment n Interaction of GMOs with biological systems n Routes of dissemination: physical; biological Risk depends upon n Nature of organism invovled n Extent of use of LMOs n End product LMO or not?

…Bio-pharmaceutical therapeutics Risk categorization of micro organisms: determining factors n Capability to cause disease n Hazard to laboratory workers n Risk of spread to community n Availability of effective treatment Health risks n Toxigenicity Pathogenicity n Allergenicity Antibiotic resistance

. . Bio-pharmaceutical therapeutics Environmental risks n Outcrossing between GMOs and pathogens n Negative effects on populations of non target organisms Risk assessment n Access n Expression n Damage Risk management and communication n Physical n Biological

GM foods: need for safety assessment n n n Expressed proteins generally not a part of regular food supply Food complex mixtures e. g. nutrients, antinutrients and natural toxins Directly enter human system Assume different forms Involve storage, processing, transportation

. . Safety assessment of GM foods comprise Guidelines by Codex Alimentarius Commission n Assessment of possible allergenicity n Assessment of possible toxicity n Compositional analysis of key components n Food processing n Nutritional modification

…. GM foods: Allergenicity; Toxicity Allergy It is a hypersensitive reaction initiated by immunologic mechanisms caused by specific substances called allergens. Assessment n Is the gene source allergenic? n Expression level of introduced gene n Unintended effect n Digestibility and heat stability Toxicity n n n New proteins as a result of intended modification Unintended new proteins as a result of the modification Natural constituents beyond their level of normal variation

…. GM foods: nutritional aspects; unintended effects n n Intended and unintended changes in nutrient levels Bioavailability of nutrients, stability and processing Presence and effect of anti-nutrients Impact of individual changes on overall nutritional profile Unintended effects Random integration of transgenes n Insertional mutagenesis n Disruption of gene functions n Production of new proteins n Changes in o Phenotype Metabolites o Enzymes Toxins o Genotype

Concluding Note…… n n n n Biosafety is integral to modern biotechnology The adoption of modern biotech products needs to be balanced with adequate biosafety safeguards Case by case scientific risk assessment and cost benefit analysis Greater acceptance of health care applications Need based adoption in GM crops and foods Participation of various stakeholders Dissemination of knowledge and information

bioethics? • as against ethics, moral issues writ large? – what is distinctive about life sciences? • is it about outcomes? – a moral judgement as to right and wrong? – who decides, and on what basis? • is it about a way of making policy choices? – consultation, consent, a broader framework? • is it a judgement on behaviour? – what kinds of research activities, ways of doing business do we favour?

IP and bioethics: law or ethics? • IP systems largely a creature of statute – Law vs. ethics: what is ethical aspect of lawmaking guided by public policy? – Ethically neutral? Or policy space for ethical considerations? – Law vs. morality: question of patentability of morally questionable technologies • ‘Natural rights’ basis for [some] IP laws and principles – Article 15. 1(c) ICESCR, Art 27. 2 UDHR • but strong utilitarian flavour to IP law and policy, increasingly emphasized in current debate on IP as a tool of public policy – Article 7, TRIPS

distinguish… • ethical aspects of a technology as such • ethical aspects of national authorities granting IP • ethical aspects of an individual seeking exclusive IP • ethical aspects of the forms of exercising IP rights

distinguish… • ethical aspects of a technology as such – e. g. the ethics of stem cell research • ethical aspects of national authorities granting IP • ethical aspects of an individual seeking exclusive IP • ethical aspects of the forms of exercising IP rights

distinguish… • ethical aspects of a technology as such • ethical aspects of national authorities granting IP – e. g. ethics of a patent office granting patents on life forms • ethical aspects of an individual seeking exclusive IP • ethical aspects of the forms of exercising IP rights

distinguish… • ethical aspects of a technology as such • ethical aspects of national authorities granting IP • ethical aspects of an individual seeking exclusive IP – e. g. ethics of a public funded agency patenting research) • ethical aspects of the forms of exercising IP rights

distinguish… • ethical aspects of a technology as such • ethical aspects of national authorities granting IP • ethical aspects of an individual seeking exclusive IP • ethical aspects of the forms of exercising IP rights – e. g. ethics of licensing patents key medical technologies).

distinguish… • ethical aspects of a technology as such – e. g. the ethics of stem cell research • ethical aspects of national authorities granting IP – e. g. ethics of a patent office granting patents on life forms • ethical aspects of an individual seeking exclusive IP – e. g. ethics of a public funded agency patenting research) • ethical aspects of the forms of exercising IP rights – e. g. ethics of licensing patents key medical technologies).

Some distinctions • Ethics and IP law and practice – In the sense of guidance for right behaviour – e. g. When is consent regarding seeking IP an ethical question? • Morality and IP law and practice – In the sense of determining innate right & wrong – e. g. substantive references to ‘morality’ in IP laws • Exclude patent protection for technologies the exploitation of which would be contrary to morality • Trademarks contrary to morality • ‘Moral rights’ in copyright and related rights

• International law: States may exclude from protection inventions on morality grounds (Article 27. 2, WTO TRIPS Agreement). • States agree to leave space for morality considerations to apply at the domestic level: – They then have the option to create a specific morality exception within their own national patent laws. – In exercising such an exception, a decision maker working within the national system may be required to undertake a specific ethical judgment about a particular technology.

distinguish… • ethical aspects of a technology as such – e. g. the ethics of stem cell research • ethical aspects of national authorities granting IP – e. g. ethics of a patent office granting patents on life forms • ethical aspects of an individual seeking exclusive IP – e. g. ethics of a public funded agency patenting research)

the BRCA gene patent

IP and bioethics: some themes • • • Transparency Consent Benefit sharing Crossover between law and morality Accommodating different value systems

Transparency in the patent system Transparency as the basis for ethical scrutiny of relevant technologies Patent information systems used to monitor: • trends and background in key technologies • state of the art in key technologies • research and patenting activities of firms/institutes/individuals But need for improved use/access of patent information, and value-added information products to guide policymaking

Traditional knowledge and IP “indigenous peoples have rarely placed anything in the so called ‘‘public domain’’, a term without meaning to us. . . the public domain is a construct of the IP system and does not take into account domains established by customary indigenous laws” - Saami Council

Traditional knowledge and IP • misuse of TK can cause severe physical or spiritual harm to the individual caretakers of the knowledge or their entire tribe from their failure to ensure that the Creator’s gifts were properly used, even if misuse was used by others outside of the tribe, or by tribal members who were outside of the control of customary authority. • For this reason. . . misappropriation and misuse [is] not simply a violation of ‘‘moral rights’’ leading to a collective offense, but a matter of cultural survival for many indigenous peoples. – Tulalip Tribes

IP and the sharing of benefits • UNBHR: equitable access to medical, scientific and technological developments as well as the greatest possible flow and the rapid sharing of knowledge concerning those developments and the sharing of benefits, with particular attention to the needs of developing countries;

IP in research agreements UNBHR: When negotiating a research agreement, terms for collaboration and agreement on the benefits of research should be established with equal participation by those party to the negotiation. (art 21. 4)

IP and bioethics in the innovation process • • research policy and planning the research phase the acquisition of IP rights the use of new technology, and exercise IP of rights

reviewing IP and bioethics issues throughout the technology development pipeline Ideally: each stage guided by an overarching conception of workable, equitable and effective arrangements for innovation in the public interest, consistent with legitimate private interests -- the ethical basis of good public policymaking?

a concluding example • many have called for an ‘open source’ approach to biotechnology • what are the bioethics-IP implications?

“should” • protection of IP “should contribute to the promotion of technological innovation and to the transfer and dissemination of technology, to the mutual advantage of producers and users of technological knowledge and in a manner conducive to social and economic welfare, and to a balance of rights and obligations. ” WTO TRIPS Agreement, art. 7

but what is the nature of that ‘should’? • “should” - as – ethical (deontological), – ethical (utilitarian), – legal (obligatory) – aspirational, or – predictive? • within legal text, guide to broader interpretation • within policy context, guide to policymaker – an heuristic?

• what message to life science policymakers? • if one should encourage or adopt ‘open source’ innovation in the life sciences – prudential – it is good for you, it serves your objective interests; – ethical: any ‘right thinking person’ would do so; – social utilitarian: – it yields overall welfare outcomes; – legal – you must do it, whether or not it is in your real or perceived interests. • Each has been made for ‘open source’ approaches to life sciences innovation. • How does the nature of the ‘should’ depend on who and where you are?

two layers of ‘should’ • essence of IP policymaking is setting what legally defined exclusivities over knowledge resources will advance innovation, fair competition and public welfare, and how those exclusivities should be shaped and governed. – some ‘open source’ ideas hard-wired at the legislative level (or can be) • individual holders of exclusive rights are also presented with a range of obligations – ethical and legal - and motivations. – when and how is there a convergence of the overall architecture of the IP system, the interests and behaviour of players within that system, and the kinds of modes characterized as open source in the life sciences?

some approaches to IP and bioethics… • bioethics within the law of patents: the scope for judgements about morality in assessments on patentability • bioethics considerations in consultations on policymaking • bioethics as a guide to practice in medical research and in business • bioethics and fundamental rights and responsibilities