Who’s Responsible If a Scientist’s Work Is Used for Harm?
A face off in medical ethics.
Are scientists morally responsible for the uses of their work? To some extent, yes. Scientists are responsible for both the uses that they intend with their work and for some of the uses they don't intend. This is because scientists bear the same moral responsibilities that we all bear, and we are all responsible for the ends we intend to help bring about and for some (but not all) of those we don't.
To not think about plausible unintended effects is to be negligent -- and to recognize, but do nothing about, such effects is to be reckless.
It should be obvious that the intended outcomes of our work are within our sphere of moral responsibility. If a scientist intends to help alleviate hunger (by, for example, breeding new drought-resistant crop strains), and they succeed in that goal, they are morally responsible for that success, and we would praise them accordingly. If a scientist intends to produce a new weapon of mass destruction (by, for example, developing a lethal strain of a virus), and they are unfortunately successful, they are morally responsible for that as well, and we would blame them accordingly. Intention matters a great deal, and we are most praised or blamed for what we intend to accomplish with our work.
But we are responsible for more than just the intended outcomes of our choices. We are also responsible for unintended but readily foreseeable uses of our work. This is in part because we are all responsible for thinking not just about what we intend, but also what else might follow from our chosen course of action. In cases where severe and egregious harms are plausible, we should act in ways that strive to prevent such outcomes. To not think about plausible unintended effects is to be negligent -- and to recognize, but do nothing about, such effects is to be reckless. To be negligent or reckless is to be morally irresponsible, and thus blameworthy. Each of us should think beyond what we intend to do, reflecting carefully on what our course of action could entail, and adjusting our choices accordingly.
It is this area, of unintended but readily foreseeable (and plausible) impacts, that often creates the most difficulty for scientists. Many scientists can become so focused on their work (which is often demanding) and so focused on achieving their intended goals, that they fail to stop and think about other possible implications.
Debates over "dual-use" research exemplify these concerns, where harmful potential uses of research might mean the work should not be pursued, or the full publication of results should be curtailed. When researchers perform gain-of-function research, pushing viruses to become more transmissible or more deadly, it is clear how dangerous such work could be in the wrong hands. In these cases, it is not enough to simply claim that such uses were not intended and that it is someone else's job to ensure that the materials remain secure. We know securing infectious materials can be error-prone (recall events at the CDC and the FDA).
In some areas of research, scientists are already worrying about the unintended possible downsides of their work.
Further, securing viral strains does nothing to secure the knowledge that could allow for reproducing the viral strain (particularly when the methodologies and/or genetic sequences are published after the fact, as was the case for H5N1 and horsepox). It is, in fact, the researcher's moral responsibility to be concerned not just about the biosafety controls in their own labs, but also which projects should be pursued (Will the gain in knowledge be worth the possible downsides?) and which results should be published (Will a result make it easier for a malicious actor to deploy a new bioweapon?).
We have not yet had (to my knowledge) a use of gain-of-function research to harm people. If that does happen, those who actually released the virus on the public will be most blameworthy–-intentions do matter. But the scientists who developed the knowledge deployed by the malicious actors may also be held blameworthy, especially if the malicious use was easy to foresee, even if it was not pleasant to think about.
In some areas of research, scientists are already worrying about the unintended possible downsides of their work. Scientists investigating gene drives have thought beyond the immediate desired benefits of their work (e.g. reducing invasive species populations) and considered the possible spread of gene drives to untargeted populations. Modeling the impacts of such possibilities has led some researchers to pull back from particular deployment possibilities. It is precisely such thinking through both the intended and unintended possible outcomes that is needed for responsible work.
The world has gotten too small, too vulnerable for scientists to act as though they are not responsible for the uses of their work, intended or not. They must seek to ensure that, as the recent AAAS Statement on Scientific Freedom and Responsibility demands, their work is done "in the interest of humanity." This requires thinking beyond one's intentions, potentially drawing on the expertise of others, sometimes from other disciplines, to help explore implications. The need for such thinking does not guarantee good outcomes, but it will ensure that we are doing the best we can, and that is what being morally responsible is all about.
Gene Transfer Leads to Longer Life and Healthspan
In August, a study provided the first proof-of-principle that genetic material transferred from one species to another can increase both longevity and healthspan in the recipient animal.
The naked mole rat won’t win any beauty contests, but it could possibly win in the talent category. Its superpower: fighting the aging process to live several times longer than other animals its size, in a state of youthful vigor.
It’s believed that naked mole rats experience all the normal processes of wear and tear over their lifespan, but that they’re exceptionally good at repairing the damage from oxygen free radicals and the DNA errors that accumulate over time. Even though they possess genes that make them vulnerable to cancer, they rarely develop the disease, or any other age-related disease, for that matter. Naked mole rats are known to live for over 40 years without any signs of aging, whereas mice live on average about two years and are highly prone to cancer.
Now, these remarkable animals may be able to share their superpower with other species. In August, a study provided what may be the first proof-of-principle that genetic material transferred from one species can increase both longevity and healthspan in a recipient animal.
There are several theories to explain the naked mole rat’s longevity, but the one explored in the study, published in Nature, is based on the abundance of large-molecule high-molecular mass hyaluronic acid (HMM-HA).
A small molecule version of hyaluronic acid is commonly added to skin moisturizers and cosmetics that are marketed as ways to keep skin youthful, but this version, just applied to the skin, won’t have a dramatic anti-aging effect. The naked mole rat has an abundance of the much-larger molecule, HMM-HA, in the chemical-rich solution between cells throughout its body. But does the HMM-HA actually govern the extraordinary longevity and healthspan of the naked mole rat?
To answer this question, Dr. Vera Gorbunova, a professor of biology and oncology at the University of Rochester, and her team created a mouse model containing the naked mole rat gene hyaluronic acid synthase 2, or nmrHas2. It turned out that the mice receiving this gene during their early developmental stage also expressed HMM-HA.
The researchers found that the effects of the HMM-HA molecule in the mice were marked and diverse, exceeding the expectations of the study’s co-authors. High-molecular mass hyaluronic acid was more abundant in kidneys, muscles and other organs of the Has2 mice compared to control mice.
In addition, the altered mice had a much lower incidence of cancer. Seventy percent of the control mice eventually developed cancer, compared to only 57 percent of the altered mice, even after several techniques were used to induce the disease. The biggest difference occurred in the oldest mice, where the cancer incidence for the Has2 mice and the controls was 47 percent and 83 percent, respectively.
With regard to longevity, Has2 males increased their lifespan by more than 16 percent and the females added 9 percent. “Somehow the effect is much more pronounced in male mice, and we don’t have a perfect answer as to why,” says Dr. Gorbunova. Another improvement was in the healthspan of the altered mice: the number of years they spent in a state of relative youth. There’s a frailty index for mice, which includes body weight, mobility, grip strength, vision and hearing, in addition to overall conditions such as the health of the coat and body temperature. The Has2 mice scored lower in frailty than the controls by all measures. They also performed better in tests of locomotion and coordination, and in bone density.
Gorbunova’s results show that a gene artificially transferred from one species can have a beneficial effect on another species for longevity, something that had never been demonstrated before. This finding is “quite spectacular,” said Steven Austad, a biologist at the University of Alabama at Birmingham, who was not involved in the study.
Just as in lifespan, the effects in various organs and systems varied between the sexes, a common occurrence in longevity research, according to Austad, who authored the book Methuselah’s Zoo and specializes in the biological differences between species. “We have ten drugs that we can give to mice to make them live longer,” he says, “and all of them work better in one sex than in the other.” This suggests that more attention needs to be paid to the different effects of anti-aging strategies between the sexes, as well as gender differences in healthspan.
According to the study authors, the HMM-HA molecule delivered these benefits by reducing inflammation and senescence (cell dysfunction and death). The molecule also caused a variety of other benefits, including an upregulation of genes involved in the function of mitochondria, the powerhouses of the cells. These mechanisms are implicated in the aging process, and in human disease. In humans, virtually all noncommunicable diseases entail an acceleration of the aging process.
So, would the gene that creates HMM-HA have similar benefits for longevity in humans? “We think about these questions a lot,” Gorbunova says. “It’s been done by injections in certain patients, but it has a local effect in the treatment of organs affected by disease,” which could offer some benefits, she added.
“Mice are very short-lived and cancer-prone, and the effects are small,” says Steven Austad, a biologist at the University of Alabama at Birmingham. “But they did live longer and stay healthy longer, which is remarkable.”
As for a gene therapy to introduce the nmrHas2 gene into humans to obtain a global result, she’s skeptical because of the complexity involved. Gorbunova notes that there are potential dangers in introducing an animal gene into humans, such as immune responses or allergic reactions.
Austad is equally cautious about a gene therapy. “What this study says is that you can take something a species does well and transfer at least some of that into a new species. It opens up the way, but you may need to transfer six or eight or ten genes into a human” to get the large effect desired. Humans are much more complex and contain many more genes than mice, and all systems in a biological organism are intricately connected. One naked mole rat gene may not make a big difference when it interacts with human genes, metabolism and physiology.
Still, Austad thinks the possibilities are tantalizing. “Mice are very short-lived and cancer-prone, and the effects are small,” he says. “But they did live longer and stay healthy longer, which is remarkable.”
As for further research, says Austad, “The first place to look is the skin” to see if the nmrHas2 gene and the HMM-HA it produces can reduce the chance of cancer. Austad added that it would be straightforward to use the gene to try to prevent cancer in skin cells in a dish to see if it prevents cancer. It would not be hard to do. “We don’t know of any downsides to hyaluronic acid in skin, because it’s already used in skin products, and you could look at this fairly quickly.”
“Aging mechanisms evolved over a long time,” says Gorbunova, “so in aging there are multiple mechanisms working together that affect each other.” All of these processes could play a part and almost certainly differ from one species to the next.
“HMM-HA molecules are large, but we’re now looking for a small-molecule drug that would slow it’s breakdown,” she says. “And we’re looking for inhibitors, now being tested in mice, that would hinder the breakdown of hyaluronic acid.” Gorbunova has found a natural, plant-based product that acts as an inhibitor and could potentially be taken as a supplement. Ultimately, though, she thinks that drug development will be the safest and most effective approach to delivering HMM-HA for anti-aging.
A new study provides key insights in what causes Alzheimer's: a breakdown in the brain’s system for clearing waste.
In recent years, researchers of Alzheimer’s have made progress in figuring out the complex factors that lead to the disease. Yet, the root cause, or causes, of Alzheimer’s are still pretty much a mystery.
In fact, many people get Alzheimer’s even though they lack the gene variant we know can play a role in the disease. This is a critical knowledge gap for research to address because the vast majority of Alzheimer’s patients don’t have this variant.
A new study provides key insights into what’s causing the disease. The research, published in Nature Communications, points to a breakdown over time in the brain’s system for clearing waste, an issue that seems to happen in some people as they get older.
Michael Glickman, a biologist at Technion – Israel Institute of Technology, helped lead this research. I asked him to tell me about his approach to studying how this breakdown occurs in the brain, and how he tested a treatment that has potential to fix the problem at its earliest stages.
Dr. Michael Glickman is internationally renowned for his research on the ubiquitin-proteasome system (UPS), the brain's system for clearing the waste that is involved in diseases such as Huntington's, Alzheimer's, and Parkinson's. He is the head of the Lab for Protein Characterization in the Faculty of Biology at the Technion – Israel Institute of Technology. In the lab, Michael and his team focus on protein recycling and the ubiquitin-proteasome system, which protects against serious diseases like Alzheimer’s, Parkinson’s, cystic fibrosis, and diabetes. After earning his PhD at the University of California at Berkeley in 1994, Michael joined the Technion as a Senior Lecturer in 1998 and has served as a full professor since 2009.
Dr. Michael Glickman