The Medawar Lecture 1998 is science dangerous?

The idea that science is dangerous is deeply embedded in our culture, particularly in literature, yet science provides the best way of understanding the world. Science is not the same as technology. In contrast to technology, reliable scientific knowledge is value-free and has no moral or ethical value. Scientists are not responsible for the technological applications of science; the very nature of science is that it is not possible to predict what will be discovered or how these discoveries could be applied. The obligation of scientists is to make public both any social implications of their work and its technological applications. A rare case of immoral science was eugenics. The image of Frankenstein has been turned by the media into genetic pornography, but neither cloning nor stem cells or gene therapy raise new ethical issues. There are no areas of research that are so socially sensitive that research into them should be proscribed. We have to rely on the many institutions of a democratic society: parliament, a free and vigorous press, affected groups and the scientists themselves. That is why programmes for the public understanding of science are so important. Alas, we still do not know how best to do this.     

Review of quantitative and qualitative studies on U.S. public perceptions of synthetic biology

How are public perceptions towards synthetic biology likely to evolve? Which factors will impact the framing of this emerging technology, its benefits and risks? The objective of this article is not to draw exhaustive conclusions about public perceptions of synthetic biology, but rather to provide readers with a review of integrated findings from the first quantitative and qualitative research ever conducted on this subject in the United States. Synthetic biology survey research shows two clear findings. The first is that most people know little or nothing about synthetic biology. Second, notwithstanding this lack of knowledge, respondents are likely to venture some remark about what they think synthetic biology is and the tradeoff between potential benefits and potential risks. Finding only some support for the “familiarity argument”—according to which support for emerging technologies will likely increase as awareness of them develops—this article suggests that analogs to cloning, genetic engineering and stem cell research appear to be recurrent in the framing process of synthetic biology. The domain of application seems to be another decisive factor in the framing of synthetic biology. Finally, acceptance of the risk-benefit tradeoff of synthetic biology seems to depend on having an oversight structure that would prove able to manage unknowns, human and environmental concerns, and long-term effects. The most important conclusion of this study is the need for additional investigation of factors that will shape public perceptions about synthetic biology, its potential benefits, and its potential risks.     

Balancing commercial and public interests

Alarge number of randomized clinical trials with important health outcomes are completed each year. Those with favorable findings are typically reported and published rapidly, while the publication of those with unfavorable results is often delayed or given a positive "spin." This observation applies primarily to industry-sponsored trials. Our objectives are to discuss the responsibility of pharmaceutical firms to the public with respect to timely, complete, and unbiased information from all randomized clinical trials and to propose solutions for improvements. We believe that in addition to financial obligations to their shareholders, pharmaceutical companies have social responsibilities to the public and to health care providers. However, private markets do not reward or compel optimal disclosure of drug safety or inferiority information on a voluntary basis.A problem which has not previously been identified relates to non-comparability of drugs. A case report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) illustrates how public interests may be violated due to failure to inform about drug inferiority. The current system for dissemination of relevant medical information could be improved if all involved parties collaborated fully. However, full disclosure of trial results is unlikely when research results are unfavorable to the firm. We conclude that expanded government regulations will be required for a satisfactory solution to the problem.     

Pre-participation screening of asymptomatic athletes

Catastrophic events, be it traffic accidents, natural disasters or homicides, always lead to scrutiny. Could we have seen the event coming and could it have been prevented? In the case of a sudden cardiac arrest of a seemingly healthy athlete the public outcry is not any different. Despite an intrinsic appeal for screening to prevent similar events, there is no evidence that justifies routine cardiovascular pre-participation screening of athletes. On balance, cardiovascular screening in athletes will most likely do more harm than good. Fatal exercise-related cardiac arrests do not occur very often. The true diagnostic yield of the pre-participation evaluation is not known and once a cardiac condition has been identified, the most appropriate intervention is often unclear. It follows that pre-participation screening of large groups of athletes without known cardiac disease will inevitably result in many false positive findings, while at the same time providing a false sense of security to those screened negative. Except for compelling reasons (e.?g. cascade screening, research settings, professional athletes), physicians should not engage in routine examination of asymptomatic athletes to prevent cardiac events.     

Risks of nutrigenomics and nutrigenetics? What the scientists say

Nutrigenomics and nutrigenetics (hereafter NGx) have stimulated expectations for beneficial applications in public health and individuals. Yet, the potential achievability of such promise is not without socioethical considerations that challenge NGx implementation. This paper focuses on the opinions of NGx researchers about potential risks raised by NGx. The results of an online survey show that these researchers (n = 126) are fairly confident about the potential benefits of NGx, and that most downplay its potential risks. Researchers in this field do not believe that NGx will reconfigure foods as medication or transform the conception of eating into a health hazard. The majority think that NGx will produce no added burden on individuals to get tested or to remain compliant with NGx recommendations, nor that NGx will threaten individual autonomy in daily food choice. The majority of researchers do not think that NGx will lead to discrimination against and/or stigmatization of people who do not comply with NGx dietary recommendations. Despite this optimism among NGx researchers, we suggest that key risk factors raised by the socioethical context in which NGx applications will be implemented need to be considered.     

The Social Value Requirement Reconsidered

It is widely assumed that it is ethical to conduct research with human subjects only if the research has social value. There are two standard arguments for this view. The allocation argument claims that public funds should not be devoted to research that lacks social value. The exploitation avoidance argument claims that subjects are exploited if research has no social value. The primary purpose of this article is to argue that these arguments do not succeed. The allocation argument has little relevance to commercial research. Social value is not necessary to avoid exploitation if subjects benefit from participation. Although the standard arguments for a social value requirement do not succeed, that view might be justified in a different way. It might be justified by appeal to the importance of social trust or the integrity of physician investigators. It is possible but doubtful that these arguments succeed.     

Giving addicts their drug of choice: the problem of consent

Researchers working on drug addiction may, for a variety of reasons, want to carry out research which involves giving addicts their drug of choice. In carrying out this research consent needs to be obtained from those addicts recruited to participate in it. Concerns have been raised about whether or not such addicts are able to give this consent. Despite their differences, however, both sides in this debate appear to be agreed that the way to resolve this issue is to determine whether or not addicts have irresistible cravings for drugs – if they do, then they cannot consent to this type of research; if they do not, then they can. This I will argue is a mistake. Determining whether or not addicts can say 'No' to offers of drugs will not help us to make much progress here. Instead we need to look at the various ways in which different types of research may undermine an addict's competence to give consent. What we will find is that the details of the research make a big difference here and that, as such, we need to steer a course between, on the one hand, painting all addicts as being unable to consent to research which involves providing them with drugs, and, on the other, maintaining that there are no problems in obtaining consent from addicts to take part in such research.     

Biodefense research: can secrecy and safety coexist?

Over the next 10 years, the United States will spend 6 billion US dollars to develop countermeasures against biological and chemical weapons. Much of this research on highly virulent pathogens will be done in academic settings around the country. This article explores the challenges in ensuring secrecy to protect national security while accommodating the right of local communities to have access to safety information regarding select agents and laboratory-acquired infections. Secrecy has been defended as being vital for protecting national security. Problems with secrecy can include the misinterpretation of intentions, particularly in laboratories located in nuclear weapons design facilities, and the restricted access to information relevant to public health and safety. While federal select agent legislation requires laboratories to have emergency plans in place with first responders, these plans do not necessarily include public health professionals, who will be responsible for any future public health action, such as quarantine, surveillance, or mass vaccinations, in the unlikely event that a laboratory-acquired infection spreads into a community. Laboratory-acquired infections do occur, even with the best safety mechanisms in place; however, the epidemiology of the incidence and severity of these infections are not known since there is no national surveillance reporting system. Evidence suggests that many of these infections occur in the absence of an actual laboratory accident. The best emergency plans and surveillance systems are only as good as the participation and vigilance of the laboratory workers themselves. Thus, laboratory workers have a responsibility to themselves and others to report all laboratory accidents and spills, regardless how minor. In addition, they should have a lower threshold than normal in seeking medical attention when feeling ill, and their physicians should be aware of what pathogens they work with to reduce the risk of a delay in diagnosis.     

A Clinical Service to Support the Return of Secondary Genomic Findings in Human Research

Human genome and exome sequencing are powerful research tools that can generate secondary findings beyond the scope of the research. Most secondary genomic findings are of low importance, but some (for a current estimate of 1%–3% of individuals) confer high risk of a serious disease that could be mitigated by timely medical intervention. The impact and scope of secondary findings in genome and exome sequencing will only increase in the future. There is considerable agreement that high-impact findings should be returned to participants, but many researchers performing genomic research studies do not have the background, skills, or resources to identify, verify, interpret, and return such variants. Here, we introduce a proposal for the formation of a secondary-genomic-findings service (SGFS) that would support researchers by enabling the return of clinically actionable sequencing results to research participants in a standardized manner. We describe a proposed structure for such a centralized service and evaluate the advantages and challenges of the approach. We suggest that such a service would be of greater benefit to all parties involved than present practice, which is highly variable. We encourage research centers to consider the adoption of a centralized SGFS.     

Parasitic diseases: opportunities and challenges in the 21st century

The opportunities and challenges for the study and control of parasitic diseases in the 21st century are both exciting and daunting. Based on the contributions from this field over the last part of the 20th century, we should expect new biologic concepts will continue to come from this discipline to enrich the general area of biomedical research. The general nature of such a broad category of infections is difficult to distill, but they often depend on well-orchestrated, complex life cycles and they often involve chronic, relatively well-balanced host/parasite relationships. Such characteristics force biological systems to their limits, and this may be why studies of these diseases have made fundamental contributions to molecular biology, cell biology and immunology. However, if these findings are to continue apace, parasitologists must capitalize on the new findings being generated though genomics, bioinformatics, proteomics, and genetic manipulations of both host and parasite. Furthermore, they must do so based on sound biological insights and the use of hypothesis-driven studies of these complex systems. A major challenge over the next century will be to capitalize on these new findings and translate them into successful, sustainable strategies for control, elimination and eradication of the parasitic diseases that pose major public health threats to the physical and cognitive development and health of so many people worldwide.     

After Dolly--ethical limits to the use of biotechnology on farm animals

The cloning of Dolly the sheep gave rise to a widespread call for limits on interference with life. Until recently, the main limits were technical: what it is possible to do. Now scientists are faced with ethical limits as well: what it is acceptable to do. In this context, we take ethics to involve systematic and rational reflection on moral issues raised in the public sphere. The concerns of the general public are not necessarily valid, but they are the best point of departure if the discussion is to lead to a socially robust framework for setting limits to the use of animal biotechnology. To assess public understanding, we examine two sources of data: Eurobarometer surveys from 1991 to 2002 and a qualitative interview study carried out in Denmark in 2000. Based on these sources, we formulate, and then discuss closely, the following concerns: dangers to human health and the environment, animal welfare, animal integrity, and usefulness. In the final part of the article, it is proposed that a principle of proportionality should be the foundation for socially robust applications of animal biotechnology. Only in cases where the usefulness of the technology can be said to outweigh countervailing moral concerns, as in biomedical research, will applications of animal biotechnology stand up to scrutiny in the public sphere.     

Bounded rationality in volunteering public goods games

It is one of the fundamental problems in biology and social sciences how to maintain high levels of cooperation among selfish individuals. Theorists present an effective mechanism promoting cooperation by allowing for voluntary participation in public goods games. But Nash's theory predicts that no one can do better or worse than loners (players unwilling to join the public goods game) in the long run, and that the frequency of participants is independent of loners’ payoff. In this paper, we introduce a degree of rationality and investigate the model by means of an approximate best response dynamics. Our research shows that the payoffs of the loners have a significant effect in anonymous voluntary public goods games by this introduction and that the dynamics will drive the system to a fixed point, which is different from the Nash equilibrium. In addition, we also qualitatively explain the existing experimental results.     

Our social genome?

Apocalyptic views on the natural order, chimeras and genetic engineering should not detract from the fact that medical research, similar to the promotion of health, is a public good. Genomics crosses all species, thereby requiring a global approach that respects human rights and public health priorities. Public trust and public participation in research demand clear stewardship as well as transparent and accountable oversight. Characterizing fundamental genomic data as a public resource might counterbalance the current overemphasis on individual rights but this will not be simple. It is only through an attachment to justice and solidarity that the dignity and well-being of persons, both as humans and as citizens, can truly be fostered.     

Decade of the brain. An agenda for the nineties.

On July 25, 1989, President George Bush, in response to reports written by the National Advisory Councils of the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health and at the urging of Congress, signed a presidential declaration designating the 1990s to be the "Decade of the Brain" and called on the United States to observe the decade with appropriate activities. At mid-decade, scientific accomplishment has been spectacular; however, both public support and increases in research resources have been minimal. It can be anticipated that scientific progress will continue to be impressive for the remainder of the decade, but many research opportunities will either not be addressed or will be postponed. At mid-decade, the time has come to re-evaluate the research agenda and the public strategy for the remainder of the decade.     

Identifying and evaluating layers of vulnerability – a way forward

“Vulnerability” is a key concept for research ethics and public health ethics. This term can be discussed from either a conceptual or a practical perspective. I previously proposed the metaphor of layers to understand how this concept functions from the conceptual perspective in human research. In this paper I will clarify how my analysis includes other definitions of vulnerability. Then, I will take the practical‐ethical perspective, rejecting the usefulness of taxonomies to analyze vulnerabilities. My proposal specifies two steps and provides a procedural guide to help rank layers. I introduce the notion of cascade vulnerability and outline the dispositional nature of layers of vulnerability to underscore the importance of identifying their stimulus condition. In addition, I identify three kinds of obligations and some strategies to implement them. This strategy outlines the normative force of harmful layers of vulnerability. It offers concrete guidance. It contributes substantial content to the practical sphere but it does not simplify or idealize research subjects, research context or public health challenges.     

Issues on research integrity: a perspective

This paper discusses several key issues that are relevant to the integrity and success of the biomedical research enterprise. Attention to these issues will improve research outcomes and reduce negative consequences in research. Subjects addressed include normative practices in research; the importance of quality data; mentoring of young scientists; how to proceed when a member of the scientific community discovers misconduct or other breaches of integrity; and the level of harm to public confidence in research due to misconduct and lack of transparency in research findings.     

Mismatched expectations

Public funding for basic research rests on a delicate balance between scientists, governments and the public. COVID could further shift this equilibrium towards translation and application.

Keeping a research laboratory well‐funded to pay for salaries, reagents, infrastructure, travel, and publications is surely a challenging task that can consume most of a PI’s time. The risk is that if the funding decreases, the laboratory will have to shrink, which means less publications and a decreased probability of getting new grants. This downward spiral is hard to reverse and can end up with a token research activity and increased teaching instead. Some would see this is as an unwelcome career change. Apart from the personal challenge for PIs to keep the income flowing, there is no guarantee that the overall funding wallet for research will continue to grow and no certainty that the covenant between the funder and the funded will remain unchanged. The COVID‐19 pandemic could in fact accelerate ongoing changes in the way public funding for research is justified and distributed.There are three legs that support the delicate stool of competitive funding. The first is the scientists or, more precisely, the primary investigators. To get to that position, they had be high achievers as they moved from primary degree to PhD to post doc to the Valhalla of their own laboratory. Along the way they showed to be hard‐working, intelligent, competitive, innovative, lucky, and something between a team player and a team leader. The judgment to grant independence is largely based on publications—and given their track record of great papers to get there, most young PIs assume they will continue to get funding. This is not a narcissistic sense of entitlement; it is a logical conclusion of their career progression.They will get started by recruiting a few PhD or higher degree students. Although this is about educating students, a PI of course hopes that their students generate the results needed for the next grant application. The minimum time for a PhD is about three years, which explains that many grants are structured around a 3‐ to 5‐year research project. The endpoints are rarely the finishing line for a group’s overall research program: Hence, the comments in reviews along the line that “this paper raises more questions than it answers and more work will be required…” Work is carried on with a relay of grants edging asymptotically to answer a question raised decades before. I recall a lecturer from my PhD days who said that he would not do an obvious experiment that would prove or disprove his hypothesis, because “If I did that experiment, it would be the end of my career”. Others are less brazen but still continue to search for the mirage of truth when they know deep in their hearts that they are in a barren desert.The funding from the competitive grants is rarely enough to feed the ever‐growing demand for more people and resources and to make provisions for a hiatus in grant income. Eventually, an additional income stream comes from industry attracted by the knowledge and skills in the laboratory. The PI signs a contract for a one‐year period and allocates some resources to deliver the answers required when due. Similarly, some other resources are shepherded to fulfill the demands of a private donor who wants rapid progress on a disease that afflicts a loved one. The research group is doing a marathon run working on their core challenges with occasional sprints to generate deliverables and satisfy funders who require rapid success—a juggling act that demands much intellectual flexibility.State funding is the second leg and governments have multiple reasons for supporting academic research, even if these are not always presented clearly. Idealistically, the public supports research to add to the pool of knowledge and to understand the world in which we live but this is not how public funding started. The first universities began as theological seminars that expanded to include the arts, law, philosophy and medicine. Naturalists and natural scientists found them a serene and welcoming place to ponder important questions, conduct experiments, and discuss with their colleagues. The influence of Wilhelm von Humboldt who championed the concept of combining teaching and research at universities was immense: both became more professional with codified ways of generating and sharing knowledge. Government funding was an inevitable consequence: initially to pay for the education of students, it expanded to provide for research activities.While that rationale for supporting teaching and research remains, additional reasons for funding research emerged, mostly in the wake of World War 2: the military, national economies, and medicine required new products and services enabled by knowledge. It also required new structures and bodies to control and distribute public resources: hence the establishment of research funding agencies to decide which projects deserve public money. The US National Science Foundation was founded in 1950 following the analysis of Vannevar Bush that the country’s economic well‐being and security relied on research. The NIH extramural program started tentatively in the late 1930s. The Deutsche Forschungsgemeinschaft (DFG) was established in 1951. The EU Framework Programmes started in 1984 with the explicit goal to strengthen the economy of the community. It was only in 2007 that the European Research Council (ERC) was established to support excellence in research rather than to look at practical benefits.But the tide is inevitably moving toward linking state research funding with return on investment measured in jobs, economic growth, or improved health. Increasingly, the rationale for government investment is not just generation of knowledge or publications, but more products and services. As science is seen as the driver of innovation and future economic growth, the goal has been to invest 3% or more of a country’s GDP into research—although almost two‐thirds of this money comes from industry in advanced economies. Even nations without a strong industrial base strive to strengthen their economies by investing in brains. This message about government’s economic expectations is not lost on the funding agencies and softly trickles down to selection committees, analysts, and program officers. The idealistic image of the independent scientist pursuing knowledge for knowledge’s sake no longer fits into this bigger picture. They are now cajoled into research collaborations and partnerships and, hooked to the laboratories’ funding habit, willingly promise that the outcome of the work will somehow have practical applications: “This work will help efforts to cure cancer”.The third leg that influences research directions is the public who pay for research through their taxes. Mostly, they do not get overly excited or concerned about those few percentages of the national budget that go to laboratories. However, the COVID‐19 crisis could change that: Now, the people in the white coats are expected to provide rapid solutions to pressing and complex problems. The scientists have so far performed extremely well: understanding SARS‐CoV‐2 pathology, genetics, and impact on the immune system along with diagnostic tests and vaccine candidates came in record time. Vaccine development moved with lightning speed from discovery of the crucial receptor proteins to mass‐producing jabs, employing many new technologies for the first time. 2020 has been a breath‐taking and successful year for scientists who delivered a great return on investment.The public have also seen what a galvanized and cooperative scientific community across disciplines can achieve. “Aha,” they may say, “why don’t you now move on to tackle triple‐negative breast cancer, Alzheimer’s or Parkinson’s?” This is a fair and challenging question. And the increasing involvement of consumers and patients in research, at the behest of funding agencies, will further this expectation until the researchers respond. And respond they will, as they have always done to every hint of what might be needed to obtain funding.The old order is changing. The days of the independent academics getting funding for life to do what they like in the manner they chose will not survive the pressures from government to show a return on investment and from society to provide solutions to their problems. The danger is that early‐stage research—I did not say “basic” as it has joined “academic” as a pejorative term—will be suffocated. Governments appoint the heads of funding agencies, and it is not surprising if the appointees share the dominant philosophy of their employer. Peer‐review committees are being discouraged, subtly, from supporting early‐stage research. Elsewhere, the guidelines for decisions on grant applications give an increasing score for implementation, translation, IP generation, and so on. Those on the panels get the message and bring it back to their institutions that slowly move away from working to understand what we are ignorant about to using our (partial) understanding to develop cures and drugs.As in all areas, balance is needed. Those at the forefront of translating knowledge into outcomes for society have to remind the public as well as the government that the practical today is only possible because of the “impractical” research of yesterday. Industry is well aware of this and has become a strong champion for excellent early‐stage research to lay the groundwork for solving the next set of hard problems in the future. The ERC and its national counterparts have a special role to play in highlighting the benefits of supporting research with excellence as the sole criterion. In the meantime, scientists have to embrace the new task of developing solutions to societal problems without abandoning the hard slog of innovative research that opens up new understanding from which flows translation into practical applications.     

Advising Patients on the Use of Complementary and Alternative Medicine

Complementary and alternative medicine (CAM) is an area of great public interest and activity, both nationally and worldwide. Many alternative medical practices have existed for hundreds, even thousands of years. Patients and professionals are turning to CAM for a variety of reasons. Most have tried conventional medicine for a particular (usually chronic) medical condition and have found the results inadequate. Some are concerned over the side effects of conventional therapies. Some are seeking out a more “holistic” orientation in health care where they can address body, mind, and spirit. A continuing challenge will be how to address CAM services that are based on time, practitioner–patient interactions, and self-care, using modern standards of evidence, education, licensing, and reimbursement. For most CAM therapies, there is insufficient research to say definitively that it works and CAM research is especially limited in the area of cancer. Given that situation, the questions (but not answers) facing the medical practitioner are clear-cut. Should the practitioner await the definitive results of formal Phase III randomized clinical trials, or should the practitioner rely on limited data, seeking out evidence that makes physiological sense and small trials that seem to offer some benefit to the patient? When and at what point do you discourage, permit, or recommend an available alternative therapy? The answers are not simple. There may be differences of opinion and values among the patient, the practitioner, and the organizations that pay for a therapy. CAM areas should be approached with every patient who enters the office recognizing that there are precautions to consider when patients are using, or plan to use, such therapies. This paper presents a broad survey of what complementary and alternative medicine is from the perspectives of both the public as user and the conventional medical practitioner, as well as provides examples of issues pertinent to understanding and evaluating research in CAM. The past is back and the future will involve integration of modern and ancient ways.     

A Practical Guide for Improving Transparency and Reproducibility in Neuroimaging Research

Recent years have seen an increase in alarming signals regarding the lack of replicability in neuroscience, psychology, and other related fields. To avoid a widespread crisis in neuroimaging research and consequent loss of credibility in the public eye, we need to improve how we do science. This article aims to be a practical guide for researchers at any stage of their careers that will help them make their research more reproducible and transparent while minimizing the additional effort that this might require. The guide covers three major topics in open science (data, code, and publications) and offers practical advice as well as highlighting advantages of adopting more open research practices that go beyond improved transparency and reproducibility.