Coronavirus

Signing Up for a COVID-19 Vaccine Trial

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Sharon Galper Grossman and Shamai Grossman

 

“Hi, Mom. I wanted to let you know that I won’t be around for the next few months. I am going to a regulated medical facility where I will receive a vaccine, wait a few weeks for it to kick in, and then receive an injection of a highly contagious, potentially lethal virus. I can’t leave the building and you can’t visit me. Don’t worry. The doctors will monitor me for signs of infection. Although there is no cure, they will give me the best treatment. I love you and am doing this for you and dad – to keep you safe from this virus.” 

This is not science fiction. Sam has joined the nearly 30,000 volunteers from over 100 countries who have offered to participate in human challenge studies for a vaccine against COVID-19.[1] A growing number of governments and their agencies recognize the value of such trials. In a bipartisan letter, 36 congressmen asked the heads of the Federal Drug Administration and the Department of Health and Human Services to consider implementing a COVID-19 human vaccine challenge trial.[2] The World Health Organization supports such studies if conducted ethically.[3]

With over 13,000,000 cases of COVID-19 worldwide and 500,000 deaths, resurgence in areas that had reduced their rate of infection, the possibility of a second wave, and no successful treatment, there is a pressing need to develop an effective vaccine to prevent infection. Traditional vaccine development involves three phases. Phase I tests vaccine safety in 15-30 patients; phase II measures efficacy in 100-300 patients, without direct comparison to a control group; and phase III, follows thousands of patients over an extensive period of time and compares the outcome of the vaccinated with that of the unvaccinated. COVID-19 vaccine studies will require at least 30,000 participants to participate for many months. These traditional methods for testing and development might not yield an effective vaccine for years. Accelerating the licensure of an effective vaccine by even a month could save thousands of lives and prevent human suffering, deeper financial loss, and further damage to the world economy.

Human challenge studies that involve the deliberate infection of healthy volunteers could substantially reduce the time to licensure and might demonstrate safety and efficacy in as few as 100 volunteers. If applied to several potential COVID-19 vaccines, this approach could maximize the efficacy of the vaccine ultimately selected for dissemination, help validate tests for COVID-19 immunity, increase our understanding of the pathogenesis of disease from exposure to infection and the duration of immunity conferred by vaccination, and the risks of transmission from infected individuals, and evaluate the efficacy of drugs for pre- or post-exposure prophylaxis in high risk populations.

This article seeks to determine how Halakhah views Sam’s participation in a COVID-19 human vaccine challenge trial.

History of Human Vaccine Challenge Trials

In 1796, in an attempt to identify an effective vaccine against smallpox, Edward Jenner conducted the first human challenge study by inoculating a healthy eight-year old with cowpox, a related but less virulent virus, and subsequently exposing him to smallpox. Jenner confirmed that inoculation had protected the child from infection. Ironically, his experiment, which would probably be considered unethical today, gave birth to the field of virology, the discovery of vaccinations, and the eradication of smallpox. Although the history of human challenge trials is complex and fraught with examples of unethical conduct,[4] more recent trials, subject to rigorous ethical standards, have substantially expedited and enhanced the efficacy and safety of vaccine development. However, to minimize the risks to infected participants, researchers generally reserve such trials for diseases with a known cure, such as cholera or malaria. No such cure exists for COVID-19, rendering a human vaccine challenge trial even more dangerous for participants like Sam.

What exactly does this participation entail for Sam?  In the preliminary stage, uninfected volunteers enter a clinical isolation facility to determine the dose of virus required to cause infection of equal severity to natural infection. Next, other uninfected volunteers, including Sam, enter the facility and are randomly assigned either vaccine or placebo. After an interval, which allows for vaccine response, both groups receive controlled exposure to the virus and intensive monitoring of infection, symptoms, and vaccine effect. If any participant develops an infection, he will receive outstanding medical care with priority for life-saving resources in a state-of-the-art medical facility with a laboratory equipped to handle the virus, appropriate airborne-infection isolation rooms, and access to an intensive care facility. Participants remain isolated in a secure and comfortable setting until they are no longer considered infectious.

Ethicists debate the morality of participating in human vaccine challenge trials. Those who object note that some volunteers will suffer serious complications or death, even if they are young, healthy, and receive cutting-edge medical treatment. They fear that vaccination might increase the severity of infection, a phenomenon associated with vaccine models for SARS.[5] In addition, the trial might not yield an effective vaccine. In addition, Sam and his fellow volunteers cannot truly provide informed consent since the dangers of the vaccine are unknown, as are the long-term risks of COVID-19 infection, including the potential for cardiac and neurologic sequelae. Even after the trial identifies an effective vaccine, it may not be generalizable to the elderly or to populations that have the greatest need for vaccination but in which it was not initially tested.[6] Furthermore, accelerating vaccine development might compromise academic rigor, leading to the release of a harmful vaccine, which could increase the public’s distrust of vaccines and refusal of standard vaccinations. Lastly, such trials could lead down a slippery slope authorizing subjects to participate in more ethically questionable studies.

Those who argue that these trials are ethical claim that participants can provide informed consent, especially since extensive media coverage of the COVID-19 pandemic has increased the public’s awareness of the dangers of infection. They point out that researchers can minimize the risks by enlisting young, healthy volunteers (ages 20-45) who are at lowest risk of death from COVID-19, from locations with a high baseline risk of infection (that is, they are likely to become infected from their natural environment, so participation only minimally increases their risk of infection and merely hastens what may be inevitable), and that the trial offers the best possible care to participants should they become infected. In addition, they argue that the level of risk involved in such studies is comparable to the risk associated with other altruistic acts that we deem ethical, such as kidney donation, firefighters running into burning buildings, and emergency medical personnel who volunteer to fight the pandemic. We allow individuals to choose dangerous professions and to engage in harmful behaviors such as smoking or riding motorcycles. We ask soldiers to go to war, notwithstanding its risk of injury or death.

A vaccine challenge trial that exposes a small group to the virus and yields information regarding vaccine safety and efficacy more quickly than a traditional phase III study can reduce the number of individuals harmed by a faulty vaccine and obtain such information more rapidly, allowing for earlier trial closure. While participation exposes volunteers to significant risks, it also offers them benefits — potential immunity to COVID-19 through vaccination or infection, possible immunity from subsequent outbreaks of COVID-19, cutting-edge medical care if necessary with priority for scarce medical resources, and reduced anxiety over infecting family and friends.

Undergoing Dangerous Medical Procedures in Halakhah

Halakhah’s approach to dangerous medical procedures begins with Avodah Zara 27b, which permits a hayei sha’ah – a sick individual with a limited time to live – to seek the care of a pagan doctor, because while we worry that a Jew-hating doctor might kill the Jewish patient, he might also effect a long-term cure. However, if the sick individual is unlikely to die, he may not turn to the pagan. The Gemara’s explanation as to why we permit the hayei sha’ah to risk his brief remaining time alive is, “le-hayei sha’ah lo haishinan” – we are not concerned about a risk to a short life because the pagan doctor might cure him.

The Gemara derives this principle from the dilemma of the four lepers in II Kings 7:3-8. Banished from their city, which was struck by famine, they faced starvation. They saw a camp of Arameans possessing food, and were confronted by the following dilemma. If they were to enter the camp, the Arameans might kill them, yet they might feed them. Preferring possible immediate death from capture to certain subsequent death from starvation, the lepers entered the camp. There they discovered an abundance of food and survived.

Tosafot (s.v. le-hayei sha’ah lo haishinan) questions the principle “le-hayei sha’ah lo haishinan.” Doesn’t Yoma 65a’s permission to move stones on Shabbat to search for a hayei sha’ah buried underneath the rubble imply that we value even the briefest survival?  Tosafot answers that in both cases we act in the best interest of the patient, rejecting certain death for an uncertainty that might prolong life. Thus, in Avodah Zarah, we disregard hayei sha’ah because otherwise the patient will surely die. In Yoma, we desecrate Shabbat for the hayei sha’ah because if we do not remove the stones, he will also certainly die. Based on Avodah Zara 27b and the story of the lepers, Shulhan Arukh Yoreh De’ah 155:1 codifies the principal “le-hayei sha’ah lo haishinan,”  permitting a hayei sha’ah to incur the risk of death at the hands of a pagan doctor in the hope of a long-term cure. Numerous modern poskim[7] rule that a hayei sha’ah may undergo a risky medical procedure if it offers the chance of a long-term cure. Shevut Ya’akov 3:75 explains, “Since the patient will certainly die, we push off the certainty of death and opt for the possibility of cure.”

One source, however, seems to prohibit the hayei sha’ah from undergoing dangerous medical treatment. Sefer Hasidim 467 describes a special herb remedy with the potential to kill or cure within days of use, accusing the women who prepared it of shortening the lives of their patients. One might interpret his denunciation as a rejection of the principle “le-hayei sha’ah lo haishinan.” Orhot Hayyim, Orah Hayyim 328:10 dismisses this interpretation, explaining that Sefer Hasidim only prohibits the risky remedy because there is an alternative safe treatment. He argues that in the absence of an effective alternative even Sefer Hasidim would accept the risk. Applied to our case ,the absence of an effective cure for COVID-19 might justify engaging in a risky process to find a cure.

Does the principle “le-hayei sha’ah lo haishinan” permit healthy volunteers like Sam to participate in a COVID-19 human vaccine challenge trial that injects half of the participants with a vaccine of uncertain benefit, exposing them to a lethal virus?  To answer this question, we must determine if hayei sha’ah applies to healthy volunteers who do not face the risk of immediate death, the level of medical risk one may incur to achieve hayei olam (long-term cure), and the level of benefit required to justify the assumption of such risk. In addition, we must establish whether the volunteers may endanger themselves, in the absence of any personal gain, purely for the benefit of others, and whether this principle applies to experimental therapies where the benefit of treatment is unclear. Finally, if Halakhah permits participation, is one obligated to volunteer?

Defining Hayei Sha’ah

The discussion permitting dangerous medical treatment assumed that the individual had the status of hayei sha’ah – a terminal illness with a limited time to live. Can we interpret hayei sha’ah more broadly, and can we apply this understanding to human vaccine challenge trials involving healthy volunteers? Rishonim and early Aharonim do not define hayei sha’ah precisely. Their interpretation of the term ranges from a life expectancy as short as one to two days to longer than a year (see Table 1). Though these poskim debate the exact duration of life required to satisfy the halakhic definition of hayei sha’ah, they view a hayei sha’ah as an individual with an illness that compromises his life expectancy. At first glance, these poskim would not classify Sam, a healthy young volunteer, as a hayei sha’ah.

However, Tiferet Yisrael Yoma, Boaz 8:3, expands the definition, permitting a healthy individual to undergo smallpox vaccination, which causes death in one in 1,000 individuals, to attain long-term immunity. He dismisses the small risk of immediate death from vaccination so as to prevent future lethal infections and broadens the definition of hayei sha’ah to include situations where the cause of death is not present, but is only a statistical possibility. He bases this ruling on Beit Yosef Hoshen Mishpat 426, which, citing the Yerushalmi Terumot, chapter eight, obligates a person to place himself in a possible danger to save his friend from a certain danger. So for example, if someone sees his friend drowning in the sea, he must jump in to save him though he risks drowning during his attempted rescue. Tiferet Yisrael reasons that if a bystander is obligated to incur possible risk to rescue his drowning friend from a possible danger, a healthy individual may accept possible immediate peril to save himself from a possible future danger.

Rabbi J.D. Bleich applies Tiferet Yisrael’s definition of hayei sha’ah to healthy carriers of the BRCA mutation who act to reduce their high risk of cancer by opting for prophylactic surgery.[8] Though the cancer has not yet developed, they may incur the immediate risk of surgery to increase their life expectancy.[9] Even if we consider a genetic predisposition or a statistical probability a present danger, it is unlikely that unafflicted carriers of such a mutation will die within twelve months. By permitting a healthy individual to assume a one in 1,000 risk of immediate death to prevent a future lethal smallpox infection, Tiferet Yisrael suggests that Halakhah recognizes the importance of disease prevention, equating it with treatments for active life-threatening disease. His halakhic analysis and assessment might permit a healthy volunteer such as Sam to participate in a COVID-19 human vaccine trial to achieve immunity from COVID-19. However, such a trial involves substantial risk without proven benefits.  In addition, because Tiferet Yisrael bases his position on the Yerushalmi which obligates an individual to endanger himself to save someone who faces certain danger, Tiferet Yisrael might even allow Sam to participate in the absence of any personal benefit, for pure altruism to save humanity. 

Defining a Permissible Level of Risk

Aharonim debate the exact level of risk the hayei sha’ah may incur. Ahiezer 2:16:6 cites Mishnat Hakhamim to permit a dangerous treatment for a safek shakul – a risk of death less than or equal to 50%. If the risk of death exceeds 50%, the hayei sha’ah may not receive the treatment. This is also the opinion of Tzitz Eliezer 10:25:5:5. If the majority of physicians endorse treatment, Ahiezer permits a risk greater than 50% and does not define the upper limit of permitted risk. Because any COVID-19 human vaccine challenge trial would receive the prior approval of an overseeing body of physicians, Ahiezer might permit participation for a risk higher than 50%. Beit David Yoreh De’ah II:340 permits a hayei sha’ah to receive a treatment that causes death in 999 out of 1,000 patients. In 1961, Rav Moshe Feinstein, Iggerot Moshe Yoreh De’ah 2:58, permitted a treatment in which the odds were more than 50% that it would cause death. However, in 1972 (Iggerot Moshe Yoreh De’ah 3:36), he modified his position, permitting only a safek shakul. He concludes that a hayei sha’ah who seeks medical treatment with a greater than 50% risk of death may rely on the more lenient position of Ahiezer and receive the dangerous therapy.

How does Sam’s participation in a COVID-19 human vaccine trial compare to the risks that these poskim cite? They address situations where the person is terminally ill and faces imminent death, but do not define the level of risk a healthy individual may incur. However, Tiferet Yisrael permits a healthy individual to undergo vaccination against smallpox with a risk of death of one in 1,000. For all adults age 20-29 infected with COVID-19, including those with comorbidities, virologists estimate a 1.1% risk of complications requiring hospitalization and 0.03% risk of death,[10] an approximation that might either overestimate or underestimate Sam’s true risk.

Sam, who suffers no comorbidities, might be at the low end of the participation risk. Furthermore, because Sam lives in an area with a large number of COVID-19 cases, he is already at high risk of infection; participation only minimally increases this. Should he become infected, he will receive state-of-the-art care, which might reduce his complications. In addition, if researchers identify an effective treatment, that treatment would further diminish his participation risk. With appropriate risk minimization (e.g., careful titration of viral dose, early diagnosis, and optimal medical care), Sam might face little, if any, additional risk related to experimental infection. Alternatively, Sam’s risk of death might be higher than estimated because the vaccine or the strain of virus injected might increase the severity of infection or the incidence of lasting harm. In addition, because the virus is so new and follow-up of those infected limited, the long-term risks of COVID-19 infection are unknown and might be greater than anticipated. Even if Sam’s risk from participating is higher than estimated, his danger of death is still well below the 50% threshold that the above poskim use and the 0.1% risk that Tifferet Yisrael permits for healthy individuals undergoing smallpox vaccination.

Definition of Hayei Olam – What Benefits Justify Risk?

The above discussion, which explored a hayei sha’ah’s acceptable level of risk with regard to medical treatments, assumed that the goal of treatment is to achieve hayei olam, a long-term cure. Poskim disagree about whether one may undergo a dangerous therapy for any other purpose, such as prolonging life in the absence of a complete recovery or the relief of pain and symptoms. Iggerot Moshe Yoreh De’ah 2:58 and 3:36 prohibits risky treatment that merely prolongs life in the absence of complete recovery. Rav Bleich offers a different perspective.[11] Quoting Ramban’s Torat ha-Adam,[12] which derives from the phrase, “le-hayei sha’ah lo haishinan” the principle that “we are not concerned with possible [loss of] hayei sha’ah in the face of more life (hayei tuva),”  Rav Bleich interprets “hayei tuva” to mean more life, and concludes that Ramban would permit dangerous medical treatment to achieve a longer period of hayei sha’ah, even in the absence of a cure. Iggerot Moshe Yore De’ah II:36 prohibits dangerous treatment for pain relief alone. Rav Yaakov Emden, Mor u-Kezi’ah 328, writes that surgery for pain relief is not “hutar le-gamrei,” categorically permitted, suggesting that under specific circumstances it might be allowed. Tzitz Eliezer 13:87 permits morphine for a dying patient, although morphine might hasten his death, because nothing torments man more than intractable pain.  Thus, Tzitz Eliezer would argue, a hayei sha’ah may undergo dangerous treatment not just to achieve hayei olam but also to achieve hayei tuva, longer life or pain relief.

What is the benefit to Sam of participating in the human vaccine challenge trial? Will participation give him hayei olam, hayei tuva, or some other non-life prolonging benefit?  First, vaccination itself or infection with or without vaccination might yield hayei olam — a long-term cure and permanent immunity to COVID-19, akin to Tiferet Yisrael’s smallpox vaccine. However, it is possible that the vaccine or infection will only provide temporary immunity. Here, participation will not achieve hayei olam, but only hayei tuva, but revaccination to boost his immunity could yield hayei olam. Second, because Sam lives in a high-infection zone, he faces a real risk of becoming infected even if he does not participate. Participation guarantees Sam priority in the allocation of medical resources and the best medical care should he become infected. By participating, Sam decreases his risk of complications and death from infection. Better care could improve his medical outcome and increase his chances of surviving COVID-19, thus facilitating hayei olam. Furthermore, if he develops immunity, he can no longer infect his family. The possibility of achieving long-term or short-term immunity to COVID-19, better treatment if infected, and relieving anxiety over infecting others are direct benefits to Sam for participating in the trial.

However, it is possible that participation will provide no benefit, direct or indirect, to Sam. Sam’s ultimate motivation for participation, like that of the thousands of volunteers who have come forward to participate in these trials, is altruism, helping to discover an effective vaccine that will save millions of lives. May one undergo a dangerous treatment in order to save others?

Incurring Risk to Save Others

Citing Talmud Yerushalmi Terumot, chapter eight, Beit Yosef Hoshen Mishpat 426 obligates one to place himself in a possible danger to save the life of someone facing certain danger. In Shulhan Arukh, Rav Yosef Karo and Rama omit this requirement. Sema Hoshen Mishpat 426:2 explains that Shulhan Arukh and Rama follow Rambam, Rif, Rosh, and Tur, who also omit this obligation. Pithei Teshuvah Hoshen Mishpat 426:2 suggests that they omitted this obligation because it contradicts Talmud Bavli (Niddah 61a and Sanhedrin 73a) and Jewish law typically follows Talmud Bavli. Radbaz 3:627 (53) was asked if a foreign government demands that a Jew undergo removal of a limb, a procedure presumed not to endanger his life,  to save the life of another Jew, may one do so.  He answers that one who consents acts with midat hasidut, a degree of piety, but if amputation will endanger his life, he is a hasid shoteh, acting illogically by violating the commandment va-hai bahem (which Sanhedrin 74a understands to mean that mitzvot are to live by and not die by). Similarly, in in Radbaz 5 Lilshonot ha-Rambam 1:582 (218), he addresses whether one is obligated to save the life of a fellow Jew, he explains that if the rescuer faces a safek mukhra – definite doubt (such as a 50% chance of harm to the rescuer and a 50% chance of safely saving the individual)- he has no obligation to act. But if the odds are greater that he will save his friend without endangering himself, failure to rescue transgresses lo ta’amod al dam rei’ekha.

Tiferet Yisrael bases his teshuvah permitting a healthy volunteer to undergo smallpox vaccination on Talmud Yerushalmi and Beit Yosef Hoshen Mishpat 426, which obligate a person to place himself in danger to save a drowning friend. Tiferet Yisrael reasons that if one may endanger himself to rescue his friend from danger, he may certainly assume risk of vaccination to save himself and achieve long-term immunity. In fact, Iggerot Moshe Yoreh De’ah 2:174:4 permits one to accept a possible danger if it will save someone else from a definite danger. Tzitz Eliezer 13:101 rules that one may participate in experimental therapy and donate blood to benefit others if physicians determine that participation is risk-free. We consider such participation a mitzvah. In this situation, however, physicians cannot determine the risk of Sam’s participating in the human vaccine trial and cannot claim that the trial is without risk.

In Yehaveh Da’at 3:84, Rav Ovadia Yosef prohibits treatment with a risk greater than 50% based on Radbaz’s classification of a rescuer who endangers himself for a safek shakul as a hasid shoteh. Rav Ovadia Yosef states that the majority of Aharonim, including Eliyah Rabba 328:8, Netziv ha-Emek She’eilah Re’eh 147:4, Aruh Ha-shulkhan 426, Mishpat Kohen 143-2, Heikhal Yitzhak Orah Hayyim 3, and Iggerot Moshe Yoreh De’ah 1:145, support this position. However, he permits kidney donation and even considers it a mitzvah, because the risk to the donor is low; according to the physicians with whom he consulted, 99% of donors recover fully from the operation. Interestingly, like Rav Ovadia Yosef, ethicists point to kidney donation as a model for determining the level of risk one may accept to benefit others[13],[14] and consider the risk of death from participation in a COVID-19 human vaccine trial equivalent to the risk of death from kidney donation.[15] Because the risk of death from participating in this trial is significantly less than 50% and is comparable to the risk of kidney donation, Halakhah would seem to permit Sam’s altruistic enrollment to save others from certain death from the virus. In fact, Sam’s participation, which has the potential to save not just one life, like a kidney donor, but millions, is not only permitted but meritorious. One might even argue that Sam is obligated to participate based on lo ta’amod al dam rei’ekha.

Rav Asher Weiss in Minhat Asher 3:122 cites Ta’anit 18b as proof that an individual may endanger himself to save the community, and in doing so performs a great mitzvah. According to Rashi, Turyanus, a Roman official, accused the Jews of murdering the emperor’s daughter. He threatened mass execution unless the guilty party confessed. To save the community, Lilianus and Pappus, falsely do so. Turyanos executes them and spares the community. Rav Weiss concludes that an individual who gives his life to save the community has a direct path to the Garden of Eden. He states that when a nation is at war, there are unique rules of pikuah nefesh, the obligation to save a life. To win, the nation requires the self-sacrifice of not only its soldiers, but all those who fill  essential, life-saving roles, such as police officers, fire fighters, security guards, and physicians. In the midst of a pandemic that has infected 13,000,000 and led to the death of 500,000 worldwide, one may reasonably conclude that we are at war with COVID-19, and that Sam and the other volunteers for a human vaccine challenge trial are voluntary conscripts.

Though Halakhah permits one to undergo risky treatment to achieve a long-term cure, poskim, including Tiferet Yisrael Yoma 8:3, do not obligate participation. If the chance that the treatment will succeed is greater than 50%, based on Iggerot Moshe in Yore De’ah 3:36 and Hoshen Mishpat 2:74:5, Rav Bleich explains that assuming risk for a long-term cure is permitted but not obligatory, because we trust a person to do what is reasonable to safeguard his body from danger. For those who are risk averse, undertaking a dangerous treatment or participating in a human vaccine trial would be unreasonable, while for the less conservative, such as Sam, the risk is acceptable.

Experimental Therapy in Halakhah

The discussion about dangerous medical treatment applies to therapies with known medical benefits. How does Halakhah approach risks incurred for experimental therapy with no proven benefit? Ttitz Eliezer 13:101 limits participation in experimental treatment to trials that are risk-free. Rav Moshe Dov Welner in ha-Torah ve-haMedinah, VII-VIII (5716-5717), 314, prohibits participation in clinical trials that lack scientific basis. He addresses a situation where the physician has no idea how to treat a disease and decides to experiment on a dying patient because the patient will die anyway. He calls such a physician a terrorist. The scientific reality surrounding human vaccine trials is vastly different than this extreme example. While the exact benefits of participation – such as whether the vaccine confers immunity and whether it will eradicate COVID-19 – are unknown, these trials employ vaccines that have already shown promise in preliminary trials and undergone extensive review by governmental and international agencies that have approved their scientific merit as potential vaccines. Such trials would not qualify as acts of desperation, implemented because the patient is dying anyway.

Minhat Shlomo 2:82:12 permits participation in medical research, classifying the battle against disease as a milhemet mitzvah, a necessary war. Today we do not have a king or beit din to declare a milhemet mitzvah against disease and obligate the healthy to take dangerous medicines to help find a cure. He writes that because recognized experts, our contemporary equivalent of a beit din or king, take great care to execute these studies, one may participate. He explains that participation qualifies as holeh lefanenu, the presence of an actual sick person before us, which is considered a fundamental halakhic requirement for defining a situation as pikuah nefesh. In Noda be-Yehuda Yoreh De’ah 280, Rav Yehezkel Landau prohibited autopsies because they are for the benefit of future patients, not those who appear before us now, and thus fail to meet a strict definition of holeh lefanenu.[16]  Rav Shlomo Zalman Auerbach explains that those autopsies were performed exclusively to increase the physician’s knowledge, so are not comparable to experimental therapy. Rav Auerbach believes that contemporary medical research qualifies as holeh lefanenu because those sick with these diseases are before us, and the treatments to be tested are before us. He considers participation in clinical trials safek hatzalat nefashot – possibly life-saving – and not merely an academic exercise to increase scientific knowledge.

Human Vaccine Challenge Trials

Recently, Rav Asher Weiss[17] directly addressed the permissibility of participating in such trials. Reiterating his position in Minhat Asher 3:122 that one may endanger oneself to perform an essential communal role such as serving as a police officer, rescue worker, or even judge who risks death threats, he permits young, healthy individuals to participate in COVID-19 human vaccine challenge trials in controlled environments because the risk of complications or death is low, especially for those who are young and lack comorbidities, and the trial can potentially save thousands of lives. He notes the concerns of Noda be-Yehuda[18] and Hatam Sofer,[19] who prohibited autopsies because such procedures failed to satisfy their halakhic definition of holeh lefanenu.  Rav Weiss explains that even if we do not define participation as pikuah nefesh, overriding biblical and rabbinic prohibitions, it is a mitzvah since it will save millions of lives. This social good permits Sam to assume the small risk of participation. Furthermore, one cannot extrapolate from the autopsies of the Noda be-Yehuda to contemporary scientific reality. It is highly unlikely that autopsies performed two hundred years ago affected medical care. He writes, “verifying the efficacy of a vaccine would not be categorized as a benefit in the distant future, but rather as a great mitzvah that is, in fact, halakhically considered to be possibly life-saving.” He rejects Rav Auerbach’s classification of medical research as milhemet mitzvah because this designation obligates participation in medical research, and Rav Weiss believes that participation is not obligatory. Only wars fought against enemy armies qualify as milhamot mitzvah, not public dangers such as wild animals and diseases, to which only the laws of pikuach nefesh apply.

Conclusion

The halakhic decisions cited above, including perhaps even Radbaz, would seem to permit Sam’s participation in a COVID-19 human vaccine challenge trial, because a healthy individual may incur a small risk of death, comparable to the risk permitted for other acts of altruism such as kidney donation to achieve long-term immunity.  In addition, the potential benefit to society is immeasurable, preventing the death and suffering of millions by halting the spread of this pandemic and ending the physical, psychological, and economic devastation of prolonged social distancing.

Table 1

Definition of hayei sha’ah According to Rishonim and Aharonim:

What is the life expectancy of a hayei sha’ah?

1-2 days

6 months

12 months

>12 months

Rashi[20]

Ahiezer[21]

Iggerot Moshe[22]

Rabbi Bleich[23]

Maharsha[24]

 

Hokhmat Shlomoh[25]

Divrei Yatziv[26]

Shevut Yaakov[27]

 

Mishpat Kohen[28]

 

 


[1] 1 Day Sooner – sign-up website for volunteers for COVID-19 Human Challenge Trials,  https://1daysooner.org/.

[2] Vaccine Letter to HHS and FDA, March 20, 2020, https://foster.house.gov/sites/foster.house.gov/files/2020.04.20_Ltr%20to%20HHS%20%20FDA%20on%20Rapid%20Vaccine%20Deployment%20for%20COVID-19%20-%20Signed.pdf.

[3] World Health Organization, “Key Criteria for the Ethical Acceptability of COVID-19 Human Challenge Studies,” May 6, 2020, https://apps.who.int/iris/bitstream/handle/10665/331976/WHO-2019-nCoV-Ethics_criteria-2020.1-eng.pdf?ua=1

[4] Presidential Commission for the Study of Bioethical Issues, “Ethically Impossible: Research in Guatemala from 1946 – 1948,” Washington, D.C. (September, 2011), https://bioethicsarchive.georgetown.edu/pcsbi/sites/default/files/Ethically%20Impossible%20(with%20linked%20historical%20documents)%202.7.13.pdf.

[5] Wan Y, Shang J, Sun S, et al., “Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry,” J Virol. 2020; 94:e02015-19.

[6] Corey, L. et al., “A Strategic Approach to COVID-19 Vaccine R&D,” Science (May 29, 2020): 948-950.

[7] Shvut Yaakov 3:75, Pithei Teshuvah Yoreh De’ah 339:1, Gilyon Maharsha Yoreh De’ah 155:1, Binat Adam 73, 93, Binyan Tziyyon 111, Tiferet Yisrael Boaz, Yoma 8:3, Ahiezer 2:16:6, Iggerot Moshe Yoreh De’ah 2:58 and 3:36, and Tzitz Eliezer 4:13, all permit a hayei sha’ah to undergo risky medical treatment for cure.

[8] Bleich, J.D., “Survey of Recent Halakhic Periodical Literature: Hazardous Medical Procedures,” Tradition, 37, no.3 (2003): 76-100, https://www.jstor.org/stable/23262430 .

[9] Bleich, J.D. “Genetic Screening: Survey of Recent Halachic Periodical Literature,” Tradition, 34, no.1 (2000): 63–87, https://www.jstor.org/stable/23261641?seq=1 .

[10] Verity, R. et al, “Estimates of the Severity of Coronavirus Disease 2019: A Model-based Analysis,” Lancet Infect. Dis. March 30, 2020, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30243-7/fulltext .

[11] Bleich, J.D., “Survey of Recent Halakhic Periodical Literature: Hazardous Medical Procedures,” Tradition, 37, no. 3 (2003): 94.

[12] Kol Kitvei ha-Ramban, II, 38.

[13] Miller, G.,  Joffe, S., “Limits to Research Risks,” J. Med. Ethics 35, 445 (2009).

[14] Resnik, D., “Limits on Risks for Healthy Volunteers in Biomedical Research,” Theor. Med. Bioeth. 33, no. 2 (April, 2012): 137.

[15] Verity, R. et al, “Estimates of the Severity of Coronavirus Disease 2019: A Model-based Analysis,” Lancet Infect. Dis. March 30, 2020, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30243-7/fulltext.

[16] For a more detailed discussion of the definition of holeh lefanenu in Covid-19, see our earlier Lehrhaus essay, https://thelehrhaus.com/scholarship/sharpening-the-definition-of-holeh-lefanenu-the-diamond-princess-and-the-limits-of-quarantine/.

[17] Rav Asher Weiss, “Experimental Treatments for Coronavirus,” Mosaica Press (2020): 5-7.

[18] Noda be-Yehuda Yoreh De’ah, 210.

[19] Hatam Sofer Yoreh De’ah, 336.

[20] Rashi Avodah Zara 27b s.v. hayei sha’ah.

[21] Ahiezer 2:16:6 explains that there is no difference between one to two day survival and six months. He classifies a patient with six months to live as hayei sha’ah, and permits him to undergo a dangerous operation in hope of a cure. It is possible that had he been asked about the status of someone with more than six months to live, he might have extended the definition of hayei sha’ah to include those with longer anticipated survivals.

[22] Iggerot Moshe Yoreh De’ah, 3:36.

[23] In Tradition, 2003, Rav J.D. Bleich argues that Hokhmat Shlomoh’s definition of one year is not rigid. He presents the example of a patient diagnosed with life-threatening leukemia and a prognosis of 13 months, who is offered a risky bone marrow transplant for cure. If he waits one month and one day for a transplant so that he now has less than one year to live and meets Hokhmat Shlomoh’s definition of hayei sha’ah, this delay will cause a deterioration of his medical condition, rendering him a much poorer candidate for the transplant, with a higher likelihood of failure than if he had undergone treatment with a life expectancy of 13 months. Rav Bleich concludes that  delaying  a life-saving though risky therapy until the individual satisfies the strict cutoff of ha yei sh’ah  is counterintuitive.

[24] Gilyon Maharsha 155:1 describes it as someone who lives “zeman mah” – a short period of time of unspecified duration.

[25] R. Shlomo Kluger, Hokhmat Shlomoh, Yoreh De’ah 155:1, derives the halakhic status of hayei sha’ah from a tereifah – a person or animal suffering a mortal wound or anomaly with less than twelve months to live, and limits hayei sha’ah to a life expectancy of less than a year.

[26] Divrei Yatziv Yoreh De’ah 219 rejects the definition of a hayei sha’ah as a tereifah, instead favoring the criteria of one who suffers from a terminal disease that will ultimately lead to death, even if death will occur after 12 months.

[27] Shevut Yaakov 3:75 addresses a situation where the individual is only expected to live one to two days. It is possible that had he been asked about the status of someone with more than six months to live, he might have broadened the definition of hayei sha’ah to include those with longer anticipated survivals.

[28] Mishpat Kohen, 144:3.

Sharon Galper Grossman and Shamai Grossman
Sharon Galper Grossman, MD, MPh, is a radiation oncologist and former faculty member of Harvard Medical School where she also obtained a Masters in Public Health. She is a graduate of the Morot L’Halakha program for women’s advanced halakha learning at Matan Hasharon. She writes and lectures on women’s health and halakha and teaches for Matan, Machon Puah and the Eden Center where she is the director of community health programming. The preparation and publication of this blog was supported by a grant from the Memorial Foundation for Jewish Culture. Shamai A Grossman, MD, MS, is vice chair for health care quality, Harvard Medical Faculty Physicians and Beth Israel Deaconess Medical Center, associate professor of medicine and emergency medicine at Harvard Medical School and a visiting professor at Sharrei Tzedek Medical Center. He has semicha from Yeshiva University and a master’s degree in medieval Jewish history. He is the author of over 200 peer reviewed publications and 4 books including Ethics in Emergency Medicine.