Risk assessment and risk management of transgenic microorganisms and viruses

This is my current response to the invitation to the Discussiion Group on risk assessment and risk management of transgenic microorganisms and viruses. But, my comment is rather general in nature and may be at least partially relevant to other LMOs.

My apology is that, on account of short notice, I had not enough time for careful draft, and I may have to change some of my comments later.



<How to apply Annex III of the Protocol when assessing the risks of transgenic microorganisms and viruses>

Annex III. Risk Assessment
Objective
1. The objective of risk assessment, under this Protocol, is to identify and evaluate the potential adverse effects of living modified organisms on the conservation and sustainable use of biological diversity in the likely potential receiving environment, taking also into account risks to human health.

Comment 1

In my personal view, interpretation of this paragraph is controversial.
1. Conservation of biological diversity: First, I recognize that the term “biological diversity” is value-laden. For example, my backyard with variety of weeds may contain more species than the well conserved garden for conservation of a rare plant species. The latter is surely more important from biodiversity conservation view point. It is not just number of species that count. Second, how we define “conservation”? Environment is constantly changing without human intervention. Rain fall, temperature, humidity, interaction among living organisms, interaction of living organisms with environment etc, they are changing every minutes affecting the life of every organism and hence “biodiversity”. You can never conserve biodiversity in the status quo. This problem relates to the point made in this inquiry “difficulties in accessing or reviewing baseline information related to the recipient and parental organisms, receiving environment, environmental interaction, etc.”  Baseline data of the last two years may not be valid for coming years, even for the next two years in the present drastic climate change.

2. Adverse effects: The term “adverse” is again value-laden. Suppose a land containing toxic metals, where we find unique fauna (biodiversity) of microbes. If the heavy metal is removed by bioremediation, the microbes living on the heavy metals may disappear and unique biodiversity will be destroyed. The bioremediation has adverse effects on the biodiversity unique to the polluted land. If the Annex is interpreted in this way, there is no room for remediation of the polluted soil.

3. The above arguments may seem stupid, but clarifying the above points is vital for this Annex to be used in the real world. In my personal view, it is important to recognize that this paragraph is value-laden and can be variably interpreted depending upon how people value the environment. Objective parameters for measuring the biodiversity may be illusory. The whole responsibility is on the shoulders of the human beings who value the environment. If this interpretation is accepted, it could be most important to agree first on biodiversity and environment that we want for the receiving environment. We should clearly identify living species and environment that we want to conserve or alter after releasing LMOs.



Use of risk assessment
2. Risk assessment is, inter alia, used by competent authorities to make informed decisions regarding living modified organisms.

Comment 2

As indicated below, risk assessment should be conducted regarding LOMs and receiving environment in combination. The term “living modified organisms” in this paragraph should be so interpreted.

 
General principles
5. Risks associated with living modified organisms or products thereof, namely, processed materials that are of living modified organism origin, containing detectable novel combinations of replicable genetic material obtained through the use of modern biotechnology, should be considered in the context of the risks posed by the non-modified recipients or parental organisms in the likely potential receiving environment.

Comment 2

1.       In my view, this paragraph is the most important paragraph in the Annex. The idea is consistent with the substantial equivalence or comparative safety assessment used in the codex’s safety assessment of the food derived from modern biotechnology.

2.       However, the phrase, “the non-modified recipients or parental organisms in the likely potential receiving environment”, may need further clarification.

3.       In the receiving environment, innumerable varieties of organisms beyond our knowledge are present. Just think of soil microbial diversity. They are interacting among themselves and interacting with environment. Soil biodiversity is important for plant growth and indirectly for animals which feed on the plants. We can never know the environment in its entirety. Assessing risk of each of the innumerable interactions of the living organisms is futile and even inappropriate for the risk assessment. One important consideration in environmental risk assessment, in my view, is to assess the organism and environment as a set by using the concept of familiarity1 developed by OECD in early 90’s.

4.       Codex alimentarius in its consideration of safety assessment of the food derived from modern biotechnology defined conventional counterpart, which is “a related plant variety for which there is experience of establishing safety based on common use as food”, which may correspond “the non-modified recipients or parental organisms in the likely potential receiving environment” in Annex III. It is important to note that this provision does not apply if LOM has no conventional counterpart(s).

5.       As no two environments are equal, if we transpose the codex conventional counterpart definition onto Annex III, the latter should be interpreted as “a related living organism already present in the receiving environment or in the like environment”. We can never know environmental processes in each detail, but we do “know” or are “familiar with” the organism and its interaction with the receiving environment despite of their instability over time. This approach may allow us more focused risk assessment (focusing on the introduced trait).

6.       For LMO’s obtained by using organisms from other places, the risk assessment should be split into two steps, assessment of the recipient organism as an organism exotic to the receiving place and assessment of genetic modification itself.

7.        The following are definitions/explanations of familiarity and substantial equivalence of OECD and codex respectively.

“Familiarity” from Safety considerations for Biotechnology: Scale-Up of Crop Plants (OECD)

-          Familiarity is not synonymous with safety; rather it means having enough information to be able to judge the safety of the introduction or to indicate ways of handling risks.

(i)                  familiarity with the characteristics of the organism, the trait introduced, the interactions between these, and the intended application.

(ii)                familiarity with the conditions and the environment into which the organisms are intended to be introduced.

(iii)              familiarity with interactions among the organism, the trait and environment.



“Substantial Equivalence” (redefined) from Guideline for the Conduct of Food Safety Assessment of Foods Derived from Modern Biotechnology (Codex Alimentarius)

-          13. The concept of substantial equivalence is a key step in the safety assessment process.  However, it is not a safety assessment in itself; rather it represents the starting point which is used to structure the safety assessment of a new food relative to its conventional counterpart. This concept is used to identify similarities and differences between the new food and its conventional counterpart2. It aids in the identification of potential safety and nutritional issues and is considered the most appropriate strategy to date for safety assessment of foods derived from recombinant-DNA plants. The safety assessment carried out in this way does not imply absolute safety of the new product; rather, it focuses on assessing the safety of any identified differences so that the safety of the new product can be considered relative to its conventional counterpart.


Methodology
8. To fulfil its objective, risk assessment entails, as appropriate, the following steps:
(a) An identification of any novel genotypic and phenotypic characteristics associated with the living modified organism that may have adverse effects on biological diversity in the likely potential receiving environment, taking also into account risks to human health;
(b) An evaluation of the likelihood of these adverse effects being realized, taking into account the level and kind of exposure of the likely potential receiving environment to the living modified organism;
(c) An evaluation of the consequences should these adverse effects be realized;
(d) An estimation of the overall risk posed by the living modified organism based on the evaluation of the likelihood and consequences of the identified adverse effects being realized;
(e) A recommendation as to whether or not the risks are acceptable or manageable, including, where necessary, identification of strategies to manage these risks; and
(f) Where there is uncertainty regarding the level of risk, it may be addressed by requesting further information on the specific issues of concern or by implementing appropriate risk management strategies and/or monitoring the living modified organism in the receiving environment.

Comment 3

General

1.       The above provisions are more appropriate for chemicals such as herbicides or insecticides than for living organisms. Differently from the case of chemical pollutants, for living organisms it is often not clear what or what level is adverse to the biodiversity and what is not (particularly in environmental use of microbes).

2.       As interpretation of terms “adverse” and “biodiversity to be conserved” depends on each person’s ethical thinking, these provisions are difficult to use in the science-based risk assessment. These terms are more appropriate for risk management.

3.       I often noticed that this paragraph is used in isolation without taking paragraph 5 into account. Any living organisms have “adverse” effects on some organisms and “beneficial” effects on other organisms. Any risk assessment should be based on this understanding. In addition, the environment and consequently biodiversity are constant changing for better or for worse without human intervention.

4.       It is important to note that these provisions should be used always with reference to paragraph 5.
Points to consider



<Experience in conducting risk assessment of transgenic microorganisms and viruses>

In my knowledge, Japan has not yet approved use of microbial LMOs in environment. I once chaired a committee that evaluates bioremediation trial with non-GM microbes. The site was a land heavily polluted by TCE. The trial revealed many interesting issues. The survival of introduced microbes and level of the pollutant never remain stable; it goes up and down. The data is highly variable depending upon the site of sampling. Rain fall dry heat greatly affected the data. I even asked myself whether the monitoring as a part of the trial ever helped the risk assessment or even it was meaningful. Another problem I experienced was the evaluation of opportunistic pathogen. A promising strain isolated from the soil was found to be a member of a species that contains a strain of opportunistic pathogen. It was finally discarded though it was the indigenous soil microbe.



<Recommendations for preparing risk assessment reports>

1. The Annex III contains paragraphs whose interpretation is quite controversial when it is applied in the real world. It causes litigation uncertainty and blocks potentially useful application of LMOs in the environment.

2. As the member countries are striving to make their regulation in line with the Cartagena protocol, it is important that the risk assessment guidance is realistic. 



<Other comments>

1. Receiving environment may need further clarification in relation to ecological niche. Even for fishes living in the free water, they are not occupying everywhere. Ecological definition of receiving environment may be needed.

2. Transgenic pharmplants could be somehow different from the other LMOs, fish, tree, microorganisms. Some of them are better suited for confined use. If such plants are planted in the field, they could be treated using the "Copy Nature Strategy" (Boulter 1993) cited in pp. 146-148 Plant Biotechnology by Slater, Scott and Fowler (identification of leads, protein purification, artificial-diet bioassay, mammalian toxicity testing, genetic engineering, selection and testing, biosafety).


Best regards,
Hiroshi