In our current pandemic, Catholic bishops sought to meet their obligation to seek alternatives to vaccines derived using cells derived from human fetuses electively aborted decades ago by publicly stating their demands for ethical vaccines to fight COVID-19. The bishops recognized the need for ending the pandemic rapidly and efficiently but, this does not mean it should be done illicitly. The Church, however, failed to become more actively engaged in this issue. The USCCB simply “asking FDA” to promote drugs that are ethically derived or with ethical prescription requirements is not an effective manner to influence the market. FDA regulates drug development but does not actively develop drugs. Thus, asking FDA to promote vaccines from ethical sources is akin to asking the USDA to promote ethically slaughtered animals for the market. It is “window dressing” not because the Bishops do not care but because they have not taken the issue seriously enough to confirm whether they are effectively engaging the marketplace. The USCCB publicized the issue as required with COVID-19 vaccine development but the pharmaceutical development of COVID-19 vaccines was not affected. Fortunately, several of these vaccines have originated from “ethical” sources due to production needs and technology advances.
Besides COVID-19 vaccines, there are numerous “opportunities” for the Catholic faithful and Church leadership to make known their disagreement and ask that healthcare systems make other types of treatments available through alternative medications or enantiomeric refinement of the current marketed drug. For drugs like teratogens, the default stance cannot be “just use birth control.” It must be in correctly forming individuals’ consciences, discerning through prayer and spiritual direction and advocating for moral solutions from the pharmaceutical industry and regulatory agencies. Masci and Smith noted at the Pew Research Center in 2018 that there were “roughly 51 million Catholic adults in the U.S.” Catholic voices can be heard but only when Catholics are willing to speak up. Catholics, holding a majority in the marketplace, have not yet been motived to vote or purchase in accordance with Catholic teachings. The recent presidential election illustrates that a candidate espousing beliefs contrary to Catholic teaching while calling himself “Catholic” did not motivate the Catholic electorate to reject him. Press clippings do not motivate the electorate any better than the pharmaceutical market. Over-the-counter medications (OTC) may be influenced by influencers, reliability, awareness, corporate image, and promotion. Pricing, cost and return on investment are the major influencers in prescription pharmaceuticals.
The Catholic challenge to COVID 19 vaccines stems from the decision to use kidney cell lines (called HEK-293) developed from aborted human fetuses or a proprietary cell line developed from retinal cells (called PER.C6) of an 18-week-old aborted fetus aborted in their development and/or testing. These cell lines tend to be used for they are available and well characterized. In the rush of a pandemic, perhaps their use was the “safest” choice to use. However, licit alternatives could have been used.
Besides HEK-293 and PER.C6 cell lines, other illicit cell lines exist. The challenge for biotechnology is that ordinary human cells can only divide between 40 and 60 times before they undergo a violent, pre-determined death. Scientists continually replenish their cell supplies with fresh ones from new animals or use cancerous cells. Cancer cells can keep growing indefinitely. Yet, cell lines from fetuses are considered the most untainted source of cells as they are less likely to contain components, such as viruses, which can contaminate vaccines or adversely affect the results of experiments.
For example, the WI-38 cell line was fundamental for the development of vaccines against polio, measles, mumps, rubella, varicella zoster (chicken pox), herpes zoster, adenovirus, rabies and Hepatitis A, as well as in the production of many early vaccines. This cell line is still used to make the rubella vaccine. Gorvett noted in BBC Future that some researchers justify the use of WI-38 to the treatments developed from this cell line may have prevented ~ 4.5 billion infections and thus, millions of lives. However, no matter how many lives were saved, it does not diminish the fact these cells were derived from an aborted fetus. In Catholic moral theology, a “good” can never be justified from an “evil.”
Virus-like particles (VLPs) were rapidly developed from influenza virus genetic sequences in order to supply vaccine such as the recombinant A (H1N1) 2009 influenza VLP vaccine. This insect cell derived H1N1 influenza vaccine candidate proved to be both immunogenic and well-tolerated in healthy adults in the midst of the pandemic in Mexico. Commercial vaccines for human use, such as Cervarix®, Provenge®, Glybera® and Flublok®, use the baculovirus expression vector system (BEVS) platform for the production of viral vaccines and gene therapy vectors. This platform used a single licit cell line to manufacture specific and safe drugs to address dangerous pathogens.
What is needed is leadership in developing alternative cell lines to replace the fetus derived lines in use today. Such lines require fundamental studies characterizing them to enable promoting their use. Alternative technologies used in COVID 19 and H1N1 vaccines need to be further developed and characterized.
Opportunities with Teratogens
Using the example of thalidomide, opportunities exist in dealing with the illicit actions required with administration of this drug. Thalidomide [α-(N-phthalimido)glutarimide] is dosed as a racemate in all medical indications approved in the United States. Yet, it was postulated that dosing with the individual (+)-(R)-thalidomide enantiomer could cause fewer teratogenic effects than the marketed racemic product. The use of stereoselective manufacturing technologies has greatly improved since thalidomide was reintroduced to the U.S. marketplace in 1998. Because of these improved technological capabilities and a desire to control the potentially differing activities of enantiomers, regulatory agencies worldwide prefer single enantiomer drug forms for chiral molecules. In fact, of the forty-five new drugs approved by FDA in 2015, all the small-molecule active pharmaceutical ingredients (APIs) containing one or more chiral centers were submitted as enantiomerically pure compounds with one exception: Lesinurad was still licensed as the racemate of two enantiomeric atropoisomers because of the hindered rotation around the single C-N bond in its naphthalene ring. No previously approved racemate was switched to single-enantiomer drug version in 2015. Thus, besides the potential issue of chiral inversion, there has been little market pressure for thalidomide to be re-registered as a single enantiomer drug. Without a suspected and uncontrolled safety issue, there is no justification for incurring such a cost.
Stereospecific Enantiomer of Thalidomide
Researchers have long been confounded by what is called the “Thalidomide paradox.” The “paradox” is in understanding why teratogenic activity is not observed in animal experiments that use (+)-(R)-thalidomide enantiomer when there is suspected in-vivo inversion. Previous studies indicate the single enantiomer form should invert and thus make the (-)-(S)-thalidomide enantiomer available to produce teratogenic defects. Thus, marketing a single enantiomer of thalidomide, rather than its racemic form, would not solve its teratogenicity.
However, researchers have proposed that when administering the (+)-(R)- isomer alone, only this isomer remains bioavailable. While the quantity of (+)-(R)-thalidomide enantiomer is reduced by inversion, whatever amount that undergoes chiral inversion is ultimately not bioavailable and the drug activity of thalidomide stems from the enantiomeric excess of (+)-(R)-thalidomide enantiomer. Hence, results of this work confirm that dosing only the specific (+)-(R)-thalidomide enantiomer may eliminate the teratogenic issue, and thereby end the need for birth control requirements with this drug.
These findings of these studies warrant further clinical studies to verify whether the teratogenic effects of thalidomide can be eliminated in-vivo solely through dosing with only the (+)-(R)-thalidomide enantiomer. Such studies require investment and direction in funding this work. If successful, no regulatory requirements for contraception would need to be promoted and the medical use of thalidomide would no longer conflict with Catholic bioethical principals. Why has this not been done? Because, as mentioned earlier, there is no market demand for such work. Contraceptive regulations are much less expensive than the clinical investigations necessary to prove this point.
The manufacturers of thalidomide do not have the incentive to run the clinical studies required for confirming the safety of such a product. Catholic universities in the United States have the capabilities to run these initial laboratory-based studies in teratogenicity. With sufficient funding, contract research concerned could execute the clinical studies as the data progresses. In the 2018-2019 academic year, the Rockne Athletics Fund at the University of Notre Dame raised $6.1 million in student athlete financial aid. Funding academic research for ethical treatments could attain these levels with a focused effort combining the universities and bishops. Notre Dame already has the Order of St. Thomas More to support the Law School and the O’Hara Society to fund graduate business studies. Georgetown University and Loyola University of Chicago have significant philanthropic efforts with their medical schools. Addressing Catholic bioethics on a pharmaceutical and medical front is solely limited by the initiative to do so.
Path Forward: Lesson from Orphan Drugs
Regulatory agencies throughout the world already have orphan drug programs in place to approve drugs with an unmet medical need by giving the industry financial incentives to address this need. Catholics, such as Melinda Gates at the Gates Foundation, invest heavily in neglected tropical diseases. They do not, however, fund projects that exclusively serve religious purposes. Eliminating the risk of contraceptive requirements of medications can be argued with safety and cost benefits beside the Catholic bioethical issues. Regardless, if orphan drug laws can be used to drive pharmaceutical innovation where the industry does not see benefit, similar regulations can be proposed to create incentives to eliminate teratogenicity in the pharmaceutical marketplace and not simply mask the issue with contraceptives.
Creating a new regulatory framework for ethical drugs is not an easy task for it requires commitment, resources and directed engagement of both the pharmaceutical industry and regulatory bodies. However, such resources do exist. While our academic institutions can fill the scientific and clinical gaps, institutions such as the Catholic Medical Association, The National Association of Catholic Nurses, Society of Catholic Scientists, International Association of Catholic Bioethics, and The National Catholic Bioethics Center have the expertise and connections to move a system for ethical drugs forward through medical and regulatory agencies.
For drugs with Catholic bioethical issues, the pharmaceutical market is going to need to be coerced. Informed consciences know that the licit path forward for the use of teratogenic drugs such as thalidomide is not birth control programs. In the case of teratogens, it should be better highlighted that contraceptive requirements have risks to the patient and women would likely prefer an alternative. Catholics must use their influence in the marketplace to demand alternatives. Yes, it is easier to write a letter to the FDA and publicize it. However, what is really needed is a concerted effort to educate the laity, influence the industry, take advantage and fund the resources at Catholic universities and oversee sponsorships of the needed trials to develop ethical alternatives in the marketplace. We have many “talents” at our disposal. (Matt 25:14-30) Are we using these talents or simply making grand gestures? Cures are not made in the confessional. Instead of simply talking of principles, Catholic bioethics should lead a call for action in making alternatives available in the marketplace. Until such replacements arrive, Catholics must reflect and pray with informed consciences to discern each individual path forward. G.K. Chesterton once said, “It isn’t that they cannot find the solution. It is that they cannot see the problem.” The real problem with vaccines for COVID 19 and teratogenic drugs like thalidomide is not that their use requires violation of principles in Catholic bioethics. The problem is that such violations have yet to engage the Church to lead in finding worthy solutions for Catholics to employ.