Neuroethical reflection in the Human Brain Project

May 15, 2019

Arleen SallesThe emergence of several national level brain initiatives and the priority given to neuroscientific research make it important to examine the values underpinning the research, and to address the ethical, social, legal, philosophical, and regulatory issues that it raises.

Neuroscientific insights allow us to understand more about the human brain: about its dynamic nature and about its disorders. These insights also provide the basis for potentially manipulating the brain through neurotechnology and pharmacotherapy. Research in neuroscience thus raises multiple concerns: From questions about the ethical significance of natural and engineered neural circuitry, to the issue of how a biological model or a neuroscientific account of brain disease might impact individuals, communities, and societies at large. From how to protect human brain data to how to determine and guard against possible misuses of neuroscientific findings.

Furthermore, the development and applications of neuro-technology to alleviate symptoms or even enhance the human brain raise further concerns, such as their potential impact on the personality, agency, and autonomy of some users. Indeed, some empirical findings appear to even challenge long held conceptions about who we are, the capacity to choose freely, consciousness, and moral responsibility.

Neuroethics is the field of study devoted to examining these critical issues. Unfortunately, it has sometimes been reduced to a subfield of applied ethics understood as a merely procedural approach. However, in our understanding, neuroethics is methodologically much richer. It is concerned not just with using ethical theory to address normative issues about right and wrong, but notably with providing needed conceptual clarification of the relevant neuroscientific and philosophical notions. Only by having conceptual clarity about the challenges presented will we be able to address and adequately manage them.

So understood, neuroethics plays a key role in the Human Brain Project (HBP). The HBP is a European Community Flagship Project of Information and Computing Technologies (ICT). It proposes that to achieve a fuller understanding of the brain, it is necessary to integrate the massive volumes of both already available data and new data coming from labs around the world. Expected outcomes include the creation and operation of an ICT infrastructure for neuroscience and brain related research in medicine and computing. The goal is to achieve a multilevel understanding of the brain (from genes to cognition), its diseases and the effects of drugs (allowing early diagnoses and personalised treatments), and to capture the brain’s computational capabilities.

The HBP is funded by the European Commission in the framework of the EU’s Horizon 2020 research-funding programme. The programme promotes responsible research and innovation (RRI). RRI is generally understood as an interactive process that engages social actors, researchers, and innovators who must be mutually responsive and work towards the ethical permissibility of the relevant research and its products. The goal is to ensure that scientific progress and innovation are responsible and sustainable: that they increase individual and societal flourishing and maximize the common good.

To develop, broaden, and enhance RRI within the project, the HBP established the Ethics and Society subproject. Ethics and Society  is structured around a number of RRI activities such as foresight analysis (to identify at an early stage ethical and social concerns), citizens’ engagement (to promote involvement with different points of view and to strengthen public dialogue), and ethics support (to carry out research in applied ethics and to develop principles and mechanisms that ensure that ethical issues raised by research subprojects are communicated and managed and that HBP researchers comply with ethical codes and legal norms).

Neuroethical reflection plays a key role in this integration of social, scientific, and ethical inquiry. Notably, in the HBP such reflection includes conceptual and philosophical analysis. Insofar as it does, neuroethics aims to offer more than assistance to neuroscientists and social scientists in identifying the social, political, and cultural components of the research. Via conceptual analysis, neuroethics attempts to open a productive space within the HBP for examining the relevant issues, carrying out self-critical analysis, and providing the necessary background to examine potential impacts and issues raised. Neuroethical reflection in the HBP does not exclusively focus on ethical applications and normative guidance. Rather, it takes as a starting point the view that the full range of issues raised by neuroscience cannot be adequately dealt with without also focusing on the construction of knowledge, the meaning of the relevant notions, and the legitimacy of the various interpretations of relevant scientific findings.

At present, the importance of neuroethics is not in question. It is a key concern of the International Brain Initiative, and the different international brain projects are trying to integrate neuroethics into their research in different ways. What continues to be unique to neuroethics in the HBP, however, is its commitment to the idea that making progress in addressing the host of ethical, social, legal, regulatory and philosophical issues raised by brain research to a great extent depends on a conceptual neuroethical approach. It enables constructive critical alertness and a thought-out methodology that can achieve both substantial scientific ground and conceptual clarity.

If you want to read more, see below a list of publications on which this post is based.

Arleen Salles

Delegates eaGNS. Neuroethics Questions to Guide Ethical Research in the International Brain Initiatives. Neuron. 2018.

Evers K, Salles A, Farisco M. Theoretical Framing for Neuroethics: The Need for a Conceptual Aproach. In: Racine E, Aspler, J., editor. Debates About Neuroethics: Springer; 2017.

Salles A, Evers K. Social Neuroscience and Neuroethics: A Fruitful Synergy. In: Ibanez A, Sedeno, L., Garcia, A., editor. Social Neuroscience and Social Science: The Missing Link: Springer; 2017. p. 531-46.

Farisco M, Salles A, Evers K. Neuroethics: A Conceptual Approach. Camb Q Healthc Ethics. 2018;27(4):717-27.

Salles A, Evers K, Farisco M. Neuroethics and Philosophy in Responsible Research and Innovation: The Case of the Human Brain Project. Neuroethics. 2018.

Salles A, Bjaalie JG, Evers K, Farisco M, Fothergill BT, Guerrero M, et al. The Human Brain Project: Responsible Brain Research for the Benefit of Society. Neuron. 2019;101(3):380-4.

How about personally optimized treatment?

May 6, 2019

Pär SegerdahlIt is well known that patients who are asked to participate in cancer trials are tempted by the therapeutic misconception. They believe they are offered a newer and better treatment, when in fact it is about research into an untested treatment. When researchers use genetic tests to develop personalized oncology, even more misconceptions can arise. I will soon explain. But first, what is personalized cancer treatment? Here is an example.

Patients whose tumor is to be operated may undergo preparatory radiation or chemotherapy. Since the preparatory therapy has severe side effects, one wants to avoid giving it to patients whose tumors do not respond to it. The challenge is to distinguish patients who respond to treatment from patients who do not. This is to be accomplished through, among other things, genetic tests on the tumor cells. If this works, you can develop personalized cancer treatment. Patients with the “right” tumor cell genetics receive the preparatory therapy, while patients who, according to the genetic tests, only get the side effects, with no effect on tumor growth, do not receive the therapy.

What are the misconceptions that can arise in patients who are asked to participate in research on personalized cancer treatment? Here are some examples.

Patients who are told that the researchers will do genetic tests can feel a genetic responsibility to participate, considering their children and grandchildren. They believe the test results may be relevant to close relatives, who may have the same disease genes. However, the tests are done on mutated tumor cells and therefore say nothing about inherited cancer risk. A sense of genetic responsibility can thus be triggered by the word “genetics” and create a genetic misconception of research in personalized oncology.

Other misconceptions have to do with the positive language used to describe personalized medicine. One talks about personally “optimized” treatments, about “tailored” treatments, about treatments that are adapted “to the individual.” This language use is not intended to mislead, but it is easy to see how words such as “optimization” can cause patients to believe that research participation means special treatment benefit.

The biggest challenge is perhaps to explain the research purpose behind the positive language. The aim is to be able in the future to distinguish between patients, to “stratify” them, as it less positively is called. Personally optimized care actually means that some patients do not receive certain treatments. This is, of course, reasonable if genetic tests can show that they have no benefit from the treatments but only get the side effects. However, what do cancer patients themselves say about stratified cancer treatment, where some patients are identified as non-responders and therefore are not offered the same treatment as other patients? Finally, do participants understand that “tailored treatment” is a future goal of the study and not something they are offered to try?

Communication with patients recruited for studies in personalized oncology faces many challenges, as patients are tempted by even more misconceptions than just the well-known therapeutic misconception.

Do you want to know more? Read the German study that inspired this blog post.

Pär Segerdahl

Perry, J., Wöhlke, S., Heßling, A.C., Schicktanz, S. 2017. Why take part in personalised cancer research? Patients’ genetic misconception, genetic responsibility and incomprehension of stratification—an empirical‐ethical examination. Eur J Cancer Care.

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Genetic risk information: lines and stage directions

April 23, 2019

Pär SegerdahlOutside of their practical contexts, simple messages quickly lose their meaning. Recall what it is like to find an old Post-it Note: “Don’t forget the disk!” – What disk? The risk is great that we invent a context. Incomprehensible messages awaken our imagination.

Similarly, messages about genetic risk need practical contexts that make the information meaningful and prevent nightmarish imaginations. The information needs to become part of a larger drama. Otherwise, we begin to fantasize: “Greatly increased risk of breast cancer.” – What do they mean, “greatly increased”? What do they mean, “breast cancer”? What do they mean, “risk”?

The difficulty of understanding and benefitting from genetic risk information is probably partly due to lack of context. The potential for generating risk information is growing rapidly. All this information is waiting for its dramas: contexts where people can ask concrete questions and get practical advice. Educational methods for explaining percentages cannot replace the loss of context. People who get genetic risk information need to know more about the disease they are at risk of developing. They may want to know if they should notify the employer of the risk. They may want to know if something can be done to reduce the risk. They may want to know what it is like to live with the disease, or with the risk of getting it. How is the family affected? Can you work having the disease? Should one worry or is it reasonable to hope that one will not get the disease? And so on.

In short, well-functioning genetic risk information has two dimensions. First, an individual dimension: “You have a greatly increased risk of…” Secondly, a general dimension: Practical instructions on a wide variety of issues that people need to know more about, and about which they otherwise begin to fantasize.

To speak the language of the theater: The individual dimension (the simple risk message) is the lines. The general dimension is the stage directions. Genetic risk information consists of both lines and stage directions.

When we discuss whether genetic risk information empowers people to influence their future health or just worries them, when we discuss the difficulty of understanding risk information, we should be clearly aware of these two dimensions of the information. Are we discussing the lines or the stage directions? Or are we discussing the lines together with the stage directions?

Which dimension of genetic risk information is most relevant to the individual? Perhaps the lines are merely a reason for moving on to the stage directions. The dramatic risk lines may speak mainly to the healthcare staff, while the individual above all needs the stage directions.

One could not work at a theater without distinguishing between lines and stage directions. Perhaps something similar applies to genetic risk information.

Pär Segerdahl

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Pragmatic trials without informed consent?

April 8, 2019

Pär SegerdahlRandomized controlled trials (RCTs) are considered to be the gold standard for determining a causal effect of medical interventions. To achieve this aim, possible confounding factors must be avoided. This implies excluding many patients from participating in the trial, for example, patients with concomitant conditions. A negative consequence of these exclusions, however, is limited generalizability. Studying the artificially uniform participant group, you will be able to determine a causal effect, but you will know much less about real-life treatment outcomes in the population where the intervention actually will be used.

Further artificiality is created by the written informed consent procedure, which excludes even further patients from participating in the trial. Moreover, because they know they participate in a clinical trial, participants may change their behavior.

All this points to the importance of so-called pragmatic randomized controlled trials. In such trials, the effectiveness of two approved and routinely prescribed medicines are compared in normal clinical practice. This avoids most of the artificiality of RCTs and significantly improves generalizability and practical clinical relevance. Randomization is still required for scientific purposes, however, and written informed consent is an ethical obligation.

The demand for written informed consent is an obstacle to pragmatic trials. By creating, once again, artificial selection of patients, results continue to be less generalizable, which detracts from the whole point of conducting pragmatic trials. In a recent paper in the BMJ, twelve authors, among them, Stefan Eriksson at CRB, therefore argue that “EU clinical trial regulations should be revised to allow the waiver or modification of informed consent in low risk pragmatic trials.”

Some would consider this suggestion to be controversial. We need to keep in mind, however, the extremely low risks of studies that compare standardly prescribed medicines in normal clinical practice. We need to balance that low risk against the enormous social value of generalizable findings in evidence-based medicine.

Pär Segerdahl

Dal-Ré, R. et al. Low risk pragmatic trials do not always require participants’ informed consent. BMJ 2019;364:l1092

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Sometimes you do not want to be taken seriously

April 1, 2019

Pär SegerdahlWhat does taking something seriously mean? Seriously, I do not think there is a given answer. A common view, however, is that serious questions must have given answers: definitive either/or answers. Without either/or answers, truth seeking degenerates into irresponsible chattering. Embryo destruction is either murder or not murder (banging one’s fist on the table). Embryo research is either permissible or not permissible (banging one’s fist on the table).

Seriousness is polarized, one could say. If I were to take polarized seriousness seriously, which seems reasonable since nothing could be more serious than seriousness itself, I would have to ask: Is seriousness polarized or not? Either it is polarized or it is not polarized! I say this resolutely, banging my fist on the table. However, the question itself is polarized. My resolution and categorical banging suddenly appear comically embarrassing. My gestures seem to run ahead of me, answering the question I thought I asked seriously by making them. What happened? Did I reach the limit of seriousness, beyond which I no longer can ask serious questions about seriousness without ending up in self-contradiction?

Perhaps I just reached the limit of small seriousness, where great seriousness can begin. Contradicting myself need not be as bad as it sounds. Perhaps I did not even know I existed until I contradicted myself. My polarized reasoning ran aground. The sunken rock was myself. Self-contradiction allowed self-discovery. For we are not dealing with two contradictory propositions, so that we must seriously investigate which of them is the true proposition and which of them is the false proposition. I was contradicted by how I myself banged my fist on the table and said, resolutely, “either-or.”

Let us be grateful for the self-contradiction. It can open our eyes to another seriousness: the seriousness of self-reflection, where we, as Confucius says, turn around and seek the cause of our failure within ourselves. Thank you, dear self-contradiction. You may be embarrassing, but just for that reason I know that I am alive and not just a propositional machine that easily can be replaced by an online chatbot!

Why do I bring up these remarkable things? Perhaps because it would be tragic if we misunderstood contemplative thinking as superfluous in an empirically founded age. Schopenhauer said something similar: “Pure empiricism is related to thinking as eating is to digestion and assimilation. When empiricism boasts that it alone has, through its discoveries, advanced human knowledge, it is as if the mouth should boast that it alone keeps the body alive.”

Trying seriously to write a blogpost about seriousness, however, is risky. For blogposts are easily circulated as mere opinions. If you were to render the content of this post, you would almost certainly be forced to polarize it as a delimited position that is either true or false. If we followed Schopenhauer’s advice, however, we would give ourselves plenty of time to quietly digest, through thinking, the strange things said in the post. Such peaceful and quiet digestion of thoughts is beyond the capacity of chatterboxes and chatbots.

Do not misunderstand my joking style. It is meant seriously to avoid being taken seriously. The Chinese thinker, Chuang Tzu, did not want to be perceived as a pedant, so he said to his audience, “I’m going to try speaking some reckless words to you and I want you to listen to them recklessly.”

Chuang Tzu was a great thinker who did not want to be taken seriously as a small one.

Pär Segerdahl

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Reality surpasses our concepts

March 20, 2019

Pär SegerdahlAfter thinking for some time about donation of human eggs and embryos to stem cell research, I want to express myself as in the headline. Reality surpasses our concepts of it. This is not as strange as it sounds. For, if our concepts already reflected reality, then no one would need to do research, or to think. Just talking would be sufficient. An endless flood of words could replace all sincere aspirations to understand life and the world.

So what is it about donation to research that makes me want to express myself as in the headline? Everyone knows that blood donation is a gift to patients. This makes blood donation humanly understandable. People want to help fellow human beings in need, even strangers. But what about donation of eggs and embryos to stem cell research? Conceptually, the donation does not go to patients in need, but to researchers. This makes it difficult to understand donation to research. Are we to assume that people feel sorry for researchers and that they therefore want to support them by donating to them? Why do donors support research?

Not only does the concept of “donation to research” make donation difficult to understand from a human point of view. The concept also causes donation to appear suspiciously exploitative. The recipient of the donation is more powerful than the donor is. Moreover, if research results are commercialized, the recipient can make a profit on the work that the donation enables, without the donor receiving any share of it. So not only does literal faith in the concept of “donation to research” make a free will to donate difficult to understand. The donation also looks suspicious. Some argue that we should prevent an increasingly capitalized life science sector from exploiting self-sacrificing donors in this way.

Nevertheless, there are people who freely donate to research. Why? I guess it often is because they use research merely as an intermediary, to be able to give to patients. The patient is equally important in donation to research as in blood donation, although the concept does not reflect this relationship. Let me give an unexpected example of intermediaries.

About one kilogram of bacteria lives in our intestinal tract. Without these bacteria, our bodies would not be able to absorb many of the nutrients in the food we eat. When we swallow the food, these bacteria are in a sense the first diners, and our bodies have to wait patiently until they have finished eating. Even if we know this, we rarely think that we are swallowing food in order to allow bacteria in the stomach to eat first. We eat without being aware of the work that these “intermediaries” in the stomach have to do, in order for the nutrients to become available to the body.

The concept of “eating” does not reflect this relationship between bacteria and us. This is not a shortcoming of the concept. On the contrary, it would be very unpleasant if the concept reflected the bacteria’s work in our guts. Who would then want to say, “Let us sit down and eat”? However, problems arise if we have too much literal faith in concepts. Our vocabulary will then begin to impose limitations on us. Our own language will shrink our otherwise open minds to mental caves, where the words cast shadows on the walls.

Researchers, then, can be seen as intermediaries between donors and patients. I hope I do not upset sensitive minds if I suggest that researchers are the bacteria that we need to make donated material available to future patients’ bodies. That is why people donate to research. They sense, more or less intuitively, that research functions as an intermediary. “Donation to research” is at heart a gift to patients.

It is even more complicated, however, for research alone cannot act as intermediary. The task is too great. For the donation to become a gift to patients, a capitalized life science sector is needed, and a healthcare system, and much else. Moreover, just as the beneficiary function of bacteria in our stomachs requires a diet that regulates the balance between bacteria, this system of intermediaries, extending from donor to patient, needs regulation and monitoring, so that all the actors work harmoniously together. We cannot allow quacks to sell dangerous or inefficient drugs to the sick, and we cannot allow researchers to access donated material in any way they see fit.

Donation to research is a striking example of how reality surpasses our concepts. When we succeed in overcoming our literal faith in concepts – when we discover the way out of the cave and see the light – then donation to research finally becomes humanly understandable. The donor uses research to be able to give to patients. Moreover, donation to research ceases to appear as a suspicious transaction between unequal parties, since the donor uses the relatively powerful direct recipient to give to a more understandable recipient: the patient. Trying to counteract exploitation by paying the donor large sums, or by giving the donor a share of the profit, would tie the donor to the wrong recipient: the one emphasized in the concept.

As mentioned, the donor uses not only research to reach the patient, but a whole system of intermediaries, such as industry, healthcare and governmental control. This system of beneficial societal bacteria is therefore, to some extent, subordinate to the donor’s will to help patients. Or rather, the subordination is an aspect of the relationship, as is bacteria’s subordination to human eating. If we want to, we can always see the opposite aspect as well. Who really eats first and who last? Who really uses whom? The questions lack definitive answers, for the aspects change into one another.

With this post, I wanted to suggest the possibility of a bigger seeing, which we can learn to use wisely in our thinking when we discover how conceptually purified standpoints easily shrink our minds to mental caves.

Pär Segerdahl

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On “truly” understanding the risk

March 12, 2019

Pär SegerdahlIt is a well-known psychological fact that people have great difficulties to understand probabilistic risks. What does it actually mean that the risk of developing breast cancer the next ten years is fifteen percent? In addition to the difficulties of understanding probabilities, mathematical expressions can cause a false appearance of exactitude and objectivity. It is often about uncertain evaluations, but expressed in seemingly definitive figures.

At our Monday seminar, Ulrik Kihlbom discussed another difficulty with understanding risk information. It can be difficult to understand not only the probabilities, but also what it is you risk experiencing. Sometimes, people face enormously complex choices, where the risks are high, but also the benefits. Perhaps you suffer from a serious disease from which you will die. However, there is a treatment, and it may work. It is just that the treatment has such severe side effects that you may die even from the treatment.

Ulrik Kihlbom interviewed physicians treating patients with leukemia. The doctors stated that patients often do not understand the risks of the treatment they are offered. The difficulty is not so much about understanding the risk of dying from the treatment. The patients understand that risk. However, the doctors said, no one who has not actually seen the side effects understand that the treatment can make you so incredibly ill.

Yet, it seems like quite comprehensible side effects: fatigue, serious infections, nausea and vomiting, stomach cramp, diarrhea, skin irritation, pain, and weight loss. Why would patients find it difficult to understand these risks?

Could it be that doctors have too high demands on “real” understanding? Must the patient, in order to “truly” understand the side effects, already have experienced the treatment? According to the doctors, experienced patients are at least easier to inform about the side effects. At the same time, the requirement that one must have had the experiences to really understand them seems too strong.

Rather, says Ulrik Kihlbom, doctors probably notice from the patients’ attitude that some of them underestimate what it is like to experience the side effects. Such attitudes can be sensed. The patients understand verbally that they are at risk of these side effects, but emotionally they do not really understand what the side effects are like, especially when they come together for a long time.

This resembles a general human difficulty. We often neglect how we ourselves are affected by our experiences. We project our present, unaffected self, and think: “I’m strong, I can handle those side effects.” However, when we actually experience the side effects, we are no longer strong! The self is not a constant, but changes with our experiences.

Here, then, it is not the probabilities that cause the difficulties, but the words. We understand the side effects verbally and can easily reproduce them. However, even words can cause a false appearance of objectivity: as if the experiences the words denote would not really reach us at our core. We separate ourselves from what we verbally understand we may experience, as if we could live our lives without being affected… without actually living them.

Ulrik Kihlbom has found a striking example of yet another aspect of the difficulty of understanding risk information. Not only probabilities but also common words such as “nausea” can create characteristic misunderstandings of risk information.

Pär Segerdahl

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