Book review: The International Law of Biotechnology: Human Rights,Trade,Patents,Health and the Environment

In Chapter One, you make reference to a 2016 open letter signed by more than 100 Nobel Laureates and other scientists who collectively called upon Greenpeace to cease and desist in their campaign against Golden Rice (a type of rice that is genetically engineered to contain high levels of the vitamin A precursor beta-carotene). ² The letter said that Greenpeace’s campaign could lead to millions of deaths from starvation. What role do you believe non-governmental organisations (NGOs) will and should have in advocating for human rights-based approaches to genetic modification?

At least in the Western world, we all experience almost every day the impact of NGOs with their environmental and climate protection mission. They are rather powerful in the Western countries, I think for several reasons. In a way, NGOs take care of our good conscience. We know there’s somebody in our society taking care of environmental protection, biodiversity, the refugee concerns, human rights concerns. From the beginning, influential environmental NGOs like Greenpeace and others have combined their mission for the ecosystem with the fight against high technologies which not only harbour risks, but also seem to interfere with the ‘natural order of things’, including biotechnology. Most of the high-profile NGOs are characterised by a single issue orientation. If you entirely focus on climate protection or on ecological or conventional agriculture, you do not worry so much about other concerns, such as the social and economic costs, employment or the nutrition of people far away in lesser developed countries. Most of the open Western societies are, in a metaphorical sense, saturated, prosperous societies. We have no problems of nutrition. Some Western countries have rather problems of overproduction in many fields of agriculture. How to nourish and how to feed our children is not a great concern, nor do we worry about our physical safety. Thus in Western societies, there’s a vast area of conscience and existential concerns that lies bare and looks for actors to take care of it. For the immediate and very urgent concerns, e.g., absence of hunger/thirst, are already taken care of. However, many NGOs focus on global commons and global issues through a parochial lens. The categoric rejection of green biotechnology in Europe reflects the cherished vision of ‘natural biotopes’, neglecting the needs of an ever-growing population on the globe. It is important to avoid challenging the self-set mandate of environmental organisations, and instead to draw the reader’s attention to the fact that we confront complex issues which call for a sensitive balancing approach.

In Europe, it is quite easy to fight against green biotechnology, especially against genetically modified (GM) crops in Germany and its neighbour countries. We have no great threats of draught, inclement cold, or pests. The corn borer exists, but it is not as big a threat to our crops as in other areas. That explains the influence of NGOs. When we look on the globe at large and the changing world order, we must realize that the Western worlds, which we tend to identify with the whole globe, are just an island, and that Europe is just an island within that island, and that Central Europe (Germany, Austria, and the Netherlands) is just an island within this European island. Many of our students, and you may have had similar experiences with your students, tend to identify their own environmental concerns, as a top priority for the rest of the world, while we have hundreds of millions which are much more concerned with access to fresh water, primary education, and the absence of physical threats because they live under entirely different conditions. The world at large often does not define human rights standards for environmental issues in the way we do in the United Kingdom, Germany, or Australia. All this is just a warning signal to look at these issues from a broader and more open perspective and to move away from a single issue focus to a balancing process.

In Chapter Two, you say ‘Consistency is an elegant, minimally invasive standard for testing the legislative decisions which interfere with human rights or other protected national interests’ ³ . Can you please elaborate on the importance of consistency, for example, do you believe there are advantages to having consistency in biotechnology laws and judgments not just within one State but also across States? Do you see any potential disadvantages of consistency in regulating biotechnology across jurisdictions, such as inflexibility? If so, are there any specific areas of biotech where there is a greater need for flexibility, as opposed to consistency?

The quoted sentence refers to legal limitations on policy options. These legal restraints may flow from a constitution, they may flow from an act of parliament, or they may flow from a human rights treaty. These standards, constitutional international standards protect certain rights, the right to family life, which is interpreted by certain human rights courts, as the freedom to opt for certain biotechnology mechanisms such as artificial insemination or in vitro fertilisation. Now the question is, what does this mean for the restraint on legislative or other policy options? It is one thing to say you must allow in vitro fertilisation because of the right to family life, or you must ban in vitro fertilisation, because on the other hand, you have the right to life of the embryo. We know that in the process of in vitro fertilisation, we have the so-called supernumerary embryos, which are just disposed because they do not have any chance to be implanted. Consistency means that each State has great discretion in allowing or banning certain mechanisms or applications of biotechnology and biomedicine. However, once they have taken a certain decision, they must act coherently and consistently. For example, there will be no interference with the State’s initial choice to allow diagnostics, genetic screening of an embryo before birth, during pregnancy or before implantation of an embryo. These are very delicate issues. An international tribunal or a supreme court will not prescribe which basic approach each State must adopt, but once they have opted for a certain decision in principle, they must move forward coherently.

If you allow prenatal screening of the embryo during pregnancy, then it would be inconsistent to ban screening methods in the pre-implantation stage, because most certainly the human beings that grow in the womb deserve at least the same protection as an embryo in vitro, which even has not yet been implanted. Or if you allow for what we call heterogeneous insemination, you cannot ban heterogeneous forms of in vitro fertilisation, meaning that a third party may intervene as a donor of sperm in one case as well as in the other. Once you allow an application in one context, you must be coherent and consistent in allowing it in a similar context. That is the argument of consistency.

Why do I find consistency an elegant principle? Because it respects the initial policy option and thus respects the democratic choice or national autonomy in taking this initial policy option. But once you have taken it, you must act rationally and coherently. You must move within the order of priorities, the order of values which you have adopted.

In Chapter Three, you introduce the precautionary principle, a principle which calls for the management and minimisation of harmful events which may materialise according to available evidence, although chains of causation are not yet reliably proven. In Chapter Six, you refer to the precautionary principle in the context of environmental issues, including GMOs and crops. As you succinctly explain, ‘the precautionary principle anticipates harmful events rather than counting on their absence’. ⁴ You stress that assessing the potential harm is no longer a purely scientific operation but also requires a value judgment. You provide the fascinating example of the decision of the German Ministry of Agriculture in 2009 to ban the cultivation of the Bt maize MON810 ⁵ (which produces toxins derived from Bacillus thuringiensis as a defence against the corn borer) because it supposedly affects the population of water fleas and ladybirds. This judgment was criticised for focusing on the more or less harmful effects of this GM crop on a species of water fleas and ladybirds, as opposed to the benefits of reducing pesticide use by thousands of tonnes. By contrast, the US understanding appears to rest on a strict scientific evaluation, such that the precautionary principle may only be relied upon where there is scientific uncertainty. For example, the US does not regulate on the basis of the assumption that GM products are per se dangerous or harbour particular risks to health and the environment. ⁶ Do you believe the American approach is more appropriate or is there greater benefit to following the more risk-averse approach of Continental Europe? What role does, or should, public opinion play in shaping this approach?

It is interesting that criticism came more from a legal/scientific audience, rather than from the public at large. Why is that so? Because there has been traditionally great reluctance towards green biotechnology in Germany. A GM tomato just looks like any other tomato. It simply has a label to denote it is ‘genetically modified’. Most Germans would be hesitant to purchase the GM tomato. Even if scientists explain that there’s no difference, taste is similar, etc. The Bt maize was rather an issue in a quite limited forum. Even in the whole European Union, we hardly have any GM crops, which by now, if you look at the global map on the use of genetic engineering in crops, you have often 50% of GM crops or more in North America and also a high percentage in South America. I think GM cotton is now dominant on a worldwide scale, GM rice is rather wide-spread etc. However, in the European Union, we are still very reluctant. And of course, our executives, in administrative agencies, or the members of our courts and Parliaments, tend to look at things through the lens of the perceptions prevailing in our societies and the socio-cultural environment. As the great lawyer Benjamin Cardozo said: ‘We may try to see things as objectively as we please. None the less, we can never see them with any eyes except our own’.

In the German case, there were two issues. The first is that these toxins, these Bacillus thuringiensis, which the maize can produce to defend itself against the corn borer, allegedly affect the population of water flees and ladybirds. That’s an assumption seriously challenged by scientists, because scientists say, well, really, the water flea and the ladybird must take up tonnes of this to have a significant impact on the population. That is the purely empiric, scientific issue. Then, we come to the second balancing issue. What is more important? The benefit of reducing pesticides or the need to save/maintain intact the population of ladybirds and water flees, regardless of their role in the ecosystem. We are talking about of thousands of tonnes of pesticides. Is it enough to say that a single species, however insignificant, is affected? That is a perspective where you have modern ‘green’ attitudes blending with very conservative attitudes: ‘Man should not interfere with the Lord’s creation’. Each species deserves protection, even if it is a mosquito that transmits malaria, an issue now discussed as ‘gene drive’.

All this is the product of some thousands of years of human manipulation in agriculture, in breeding cattle, dogs, and horses. But many of us still follow, quite understandably, the concept of original creation not to be interfered with. Although nature, as we see it, is a product of human history. These attitudes still linger around and that explains why up to now the European Union has been so reluctant, because of this defensive socio-cultural attitude where modern ecologist positions are united with very conservative, often religiously inspired, positions forming an alliance against modern technologies. Now, very recently, there is a gradual change also in public perceptions, as we see the benefits of biotechnology. Much of it is associated with genome editing, where we see that with fairly precise operations, we can enhance productivity, for example, resistance against pests, and can reduce the use of fertilisers. Even in the field of human gene therapy, we see changes in ethical and political postures.

This change is driven by several factors. The benefits in terms of an ecological balance or in curing hereditary diseases emerge more clearly than in the past. An important factor in the changing European approach is the promising developments in the field of genome editing. There is a consultation process going on, ⁷ and the European Commission is considering a more liberal approach. The traditional European approach rests on the assumption that modifying the genome, genetic engineering as such, is a risky undertaking. From an empirical perspective, this assumption does not stand up to scrutiny. As most scientists would tell us, the risk is not created by the technique of genetic engineering. It depends on the organisms and the DNA sequences involved. It is the product that matters, either the initial organism or the modified organism, rather than the procedure. That is the American approach, and the approach taken in many other countries. There are quite a number of countries that do not have very tight regulation at all or do not apply the regulations they have. Using a systematic approach from what I would call the competition among regulatory systems, scientifically speaking, the US model seems to trump the European model.

Unlike individuals, legislators and other public authorities should be guided by objective risk assessment and risk evaluation rather than by personal preferences.

In Chapter Four, you refer to various international human rights instruments and international treaties which are specifically dedicated to the bioethical dimensions of human rights (including personal autonomy and self-determination (the principle of informed consent), the right to privacy, and non-discrimination). How effective do you believe these instruments and treaties have been, and will be, in minimising the risk of misusing biotechnology (such as in vitro fertilisation, human stem cell techniques, predictive genetic testing, genetic engineering, and human cloning) and infringing on human rights? Would universal standards / a universal approach to human dignity be more beneficial than a nation-centred approach?

I think that’s a very sensitive area. And why is that so? It is so that even within our societies, these issues are very contested. Shall we allow human stem cell research? A very controversial issue. Stem cell research is allowed, even with embryonic human stem cells, in a number of European countries. Yet, they are banned in others, and some take an intermediate position such as Germany. We do not allow the production of human stem cell lines. We say it goes against human dignity to use an embryo, even a supernumerary embryo from in vitro fertilisation to produce a line of stem cells. Still, we recognize that stem cell research may be very beneficial in curing serious diseases. What have we done in Germany? We say, well, there’s an absolute ban on producing these stem cells in Germany, but we allow the importation of these stem cells under certain conditions from the UK, Israel and other countries. If we have such a contrasting approach, such controversy, even within a country, it will be very difficult to reach consensus on a regional level. We have the European Convention on Biomedicine, which tries to reign in certain applications, including of biotechnology, and we have additional protocols.

Just to highlight the difficulties which we have in Western democracies, I will give you the case of Costa Rica on fertilisation. A Government decree allowed in vitro fertilisation under certain conditions in Costa Rica but the constitutional chamber of the Supreme Court subsequently struck this decree down. ⁸ The Court found that this goes against the protection of human life, the life of the embryo, and also against the American Convention on Human Rights, which they interpreted as containing a guarantee to protect human life. In the Supreme Court’s interpretation, the American Convention prohibits in vitro fertilisation. Prospective parents were granted a hearing before the Inter-American Court of Human Rights which held the American Convention on Human Rights, in the Court’s interpretation, gives parents a right to have recourse to in vitro fertilisation because the right to family life and the options under this right trump the protection of human life as understood by the Costa Rican Court. But Costa Rica did not swiftly implement this decision. That is quite understandable because it is such a difficult issue. Neither the Costa Rican Constitution nor the American Human Rights Convention mentions in vitro fertilisation. It does not make any reference to modern biotechnology because it did not exist at the time.

My point is beware of overdeveloping or overinterpreting legal instruments, and leave policy/democratic choices a sufficient margin for swaying one way or the other. Another example would be the United Nations Declaration on Human Cloning. But even cloning, which is one of the very rare cases where we would assume that it is easy to reach consensus at a global level, ended up with a very lukewarm formula. The Declaration adopted by the UN General Assembly did not say the cloning of human beings should be banned. It said that the cloning of humans should be banned as far as it violates human dignity. Now that begs the question, when does it violate human dignity? All of us have differing conceptions about human dignity which are framed by our socio-economic background. We see this with human rights. Our European Court of Human Rights is quite proactive, maybe even activist. But in the area of biotech, it acts very carefully. Judges shun away from the question of whether the life of the unborn is protected because they know that even within this European family, which is a rather homogeneous family, we have splits and rifts, which make it difficult to impose a generally recognised common human rights standard, and ever more difficult at a global level. I ultimately believe human rights can give some guidance within the confines of consistency.

In Chapter Five, you note that ‘the prohibition of germline therapy established in many countries will come under new, intense scrutiny as soon as scientific progress makes such treatment a promising medical option to address hereditary diseases and allows the risks of unintended side effects to be reliably controlled’. ⁹ What legal measures do you believe should be adopted to regulate the use of germline therapy in an ethical manner? How do you envision the role of international organisations, such as the World Health Organization (WHO), in establishing global guidelines and standards for germline therapy laws?

The World Health Organization, having such a global membership, would focus more on the risk from a health perspective, which is one aspect in germline therapy. You will remember a Chinese scientist claimed to have applied this germline therapy in a case where both parents were suffering from AIDS. ¹⁰ There was a very harsh reaction, even in China. We see germline therapy as something going to the very core of man interfering with the natural heritage. Changing the genome of a human being in a way that is passed on to future generations is considered as much more serious than manipulating crops or dogs or cattle or rice. There are other implications, such as enhancement, e.g. it might be abused for enhancement rather than addressing serious diseases.

Germline therapy has two sides. One is the risk of adverse, collateral side effects. You address a part of the human genome to weed out bad gene/s for a serious disease. You may succeed but by doing so, you produce an unintended change because the DNA encodes for proteins with many functions; thus, you may target one function intentionally, but unintentionally you target another function, and you knock out another function, which is a very important beneficial function. That is one issue, that is the medical implication. The other issue is the ethical, religious implications. In the past, the ethical concerns and the medical concerns stayed together. Thus, many critical voices who were opposed for religious reasons heavily relied, in addition, on the medical implications, on the unintended collateral side effects. But as science moves on, we are gradually approaching the moment where we possibly can control the medical side effects, which means that the opposition against germline therapy is thrown back entirely to the ethical concern, as the medical concern will be taken care of. And then, things become difficult and you see that reflected in the positions taken by many European ethical councils.

In the past, there were many calls for a moratorium on germline therapy in Europe and the United States. At the time that made sense, because even those who did not share the ethical concerns may have shared the medical concerns. Now, the German Ethical Council, and others in Europe take a rather cautious approach and say it is a difficult issue. It is an issue which calls for balancing. We must take care of the medical side. But once that can be controlled, we must re-engage in a discussion on whether the ethical side is sufficient to support a ban. Indeed, that is my personal opinion, but I voice it with care. I do not think that human dignity as such should guarantee the existence of severe hereditary diseases. I find it difficult to link the survival of hereditary disease, serious hereditary diseases, including diseases which lead to the death of a child after a few months, with human dignity. I believe that approach is becoming a growing tendency also in the Western world. But again, here we have weighty religious, ideological underpinnings.

I think we can, at an international level, to come back to your question, reach consensus on the empiric, scientific side, on the medical implications. But it will be very difficult to reach consensus on the ethical implications because we have differing religious, socio-economic backgrounds.

In Chapter Eight, you discuss biotechnology and international trade law. You focus on the impact and interpretation of relevant agreements of the World Trade Organisation (WTO) in relation to biotechnology products. What do you see as the future of the WTO’s role in regulating biotechnology trade, especially as new inventions continue to emerge and reshape global markets?

I see essentially two implications. One is providing tools to scrutinize interference with the admission of biotech products in the interest of health. We have the General Agreement on Tariff and Trades, ¹¹ which liberalises international trade; and we have the Agreement on Sanitary and Phytosanitary Measures, ¹² which allows the taking of restrictive measures against imported products in the interest of protecting human health but only based on available scientific evidence and in terms of proportionality. Proportionality brings us again to the issue of consistency. That injects a very strong empiric dose in international trade in the area of biotech products because you can take restrictive measures, which may also consist in a complex authorisation process, but it must be justified by scientific evidence. There must be sound evidence or at least defensible, sustainable evidence that there may be something in these products which is harmful to human health or to animals or to the ecological environment, the prevention of pests.

The second dimension are patents, which are inspired very strongly by the US-American approach. We also have the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), ¹³ which says, in principle, there must be patents available for all inventions subject to public morals. That is a very broad obligation in favour of patents, which raises problems when we have biotechnology products which are relevant in addressing pandemic diseases. Once you have a patent, you can influence the conditions under which your product is marketed, including the price, either by selling it directly or by granting licences. There we have the issue that becomes relevant with respect to patented biotechnology medicines or vaccines that we allow exceptions, especially for poorer countries that have to manage a pandemic like the COVID crisis. That is an issue in terms of maintaining this balance between the legitimate interests of the industrialised status of patent holders and the legitimate interests of developing countries which are affected by these diseases.

In Chapter Nine, you refer to the patentability of genetic mutations and the famous case of Myriad Genetics’ attempt to patent BRAC1 mutations. An interesting recent development in this area is that US Senators have reintroduced the Patent Eligibility Restoration Act (PERA) which would expressly permit the patenting of a human gene or other natural material if it is isolated, purified, enriched or otherwise altered by human activity or otherwise employed in a useful invention or discovery (although the Bill excludes unmodified human genes as they exist in the body and unmodified natural materials as they exist in nature from being patented). ¹⁴ So it would essentially reverse the 2013 Supreme Court decision in Myriad ¹⁵ (making both newly discovered human genetic variants and pathogenic genomes patentable again). It would set the US apart from other jurisdictions, such as Australia. ¹⁶ However, it would bring the US more in line with EU legislation, where you can obtain a patent for isolating a human or plant gene. ¹⁷ This is one of the few cases where European law is more ‘liberal’ than US legislation. Which is the better approach?

You’re quite right that this is one of the very few areas where European law is more ‘liberal’ in allowing a patent for the mere isolation of a DNA, of a gene sequence. If you look at the decision of the US Supreme Court, ¹⁸ you will understand why I recommend it to my students because it brings everything together clearly. It sets the biological background and then applies to this background, the legal framework. We can grant patents only on inventions. We can’t grant a patent on a discovery. Columbus may have ‘discovered’ America, but he certainly didn’t invent America. It was something pre-existing. One argument was, if you’re trying to just isolate human genes, you didn’t invent the genes. In this case, a parallel was drawn to a microscope where you may find a virus or a Bacillus but this again is a discovery, it’s not an invention. Whilst the Europeans say there’s an inventive step in the extraction, because the extraction is more than mere discovery. I’m very reluctant to side with the European point of view because I think that there’s not much added value in the mere extraction of a gene. There may be, and I believe there is, added value in modifying a pre-existing gene sequence, in synthesising it. In addition, you must indicate the industrial values of the application. This requires you to describe the function of a DNA sequence when you claim a patent.

There is a position which we have adopted in the meantime in Germany and elsewhere, and I strongly advocated at the time, ¹⁹ that we limit a patent right to the functions that were disclosed in the patent application, because very often you have multifunctional gene sequences. That happened very often in the past that a patent holder revealed a certain genetic function which was useful but behind that lay another, far more important function, and they would reap with their patent, the benefits associated with this additional function as an underserved windfall. It would be appropriate to say in the case of human DNA, the patent only covers the functions which are revealed and what you did not find out and did not describe is not covered by the patent application. Coming back to the Myriad case, if you hold the patent on the breast cancer gene, that is just like a licence to print money. Because all the screening, all these operations, applications in a way must be based on a licence. Citing Myriad, I would say, we must look at the added value. I do not see it that much in the mere isolation. There may be an added value and there probably is in synthesising and modifying DNA sequences with a new function. I am not sure that this bill will be passed as an Act of Congress because there are too many stakeholders, and very often in these patents related to human DNA, you create cross-dependencies. They’re a very complex issue. One should really convince themselves that there is added value, which was created by inventing something: a technique of synthesising, producing, modifying, plus an industrial application.

Biotechnology is being harnessed in tort litigation. Both plaintiffs (claimants) and defendants have relied on genetic test results as a means of proving or disproving causation or discounting damages in medical negligence claims, workers’ compensation claims, motor vehicle accident claims, and toxic tort claims. ²⁰ What is your opinion on the application of genetic test results in civil litigation? Is the scientific understanding of genetics at the stage where it should be used in civil trials (when determining causation and/or at the stage of determining damages/compensation)? In addition, biotechnology is also being harnessed in criminal law. You may be familiar with a very recent Australian example involving the release of Kathleen Folbigg after an inquiry considered evidence that a genetic mutation more likely than not caused the death of her children, rather than homicide. ²¹ What is your opinion on these applications of genetic test results in criminal litigation? Is genetics at the stage where it should be used in criminal trials (when determining causation and/or sentencing)?

We in Germany and Europe in general are very careful about these predictive tests and genetic tests as well, because we assume that it’s not only a right to know, but a right not to know. Insurance companies and other private actors cannot have access to this data, cannot oblige you to undergo this genetic screening if you are not happy with it. That’s part of individual autonomy. I think that should also apply in tort cases and even in criminal cases. But of course, in many cases, it may be the defendant himself or herself that has an interest in having this genetic disposition to say causing damage was not their responsibility because it was a pre-established disposition. For example, in medical negligence cases, the patient would have died or contracted the illness anyhow, or in criminal cases, the defendant would not be responsible because they have a predisposition. I do think in this context, human dignity or other human rights concerns do not stand in the way of having access to this genetic screening. I think it all goes back to individual autonomy. Of course, this issue is complex because if we don’t have access to genetic screening, we still investigate whether the mother, grandfather, or great-grandfather suffered from a disease? Then in the absence of genetic screening, you may make plausible conclusions which are unfavourable to them. Though it’s a very complex issue, I believe as an issue of the law of criminal or civil procedure, the principle of individual autonomy should be respected.