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Good Science for a Better World

The sequencing of the human genome has ushered a renaissance in biotechnology.  Our understanding of genetic information and advancements in biotechnology are creating therapies and vaccines that will transform pharmaceuticals and health care.  Many of these products are developed and/or manufactured using ethically objectionable cell lines harvested from aborted fetal tissue.  Agathos Biologics is on a mission to create ethically acceptable products so that everyone—researchers, physicians, and ultimately patients—can benefit from these novel technologies without compromising their moral beliefs.

 

Background and History of Cell Lines Used for Biological Research and Manufacturing

The sequencing of the human genome was declared complete on April 14, 2003(1), two years earlier than planned, and was a watershed event in biotechnology.  Given that the sequencing of the human genome provided the ability to “read” genes of a patient, one might say that a significant direct therapeutic benefit would be the creation of a therapy that “wrote” a gene to correct a defect.  This concept of “gene therapy” long predated the human genome project, but the project certainly accelerated its progress.  The first gene therapy approved in the Western world was Glybera in July 2012.  Glybera, using an engineered virus as a vector, delivered the gene for the enzyme lipoprotein lipase to the cells of patients with lipoprotein lipase deficiency, a genetic disorder in which a person has a defective gene for the enzyme.  Although it is no longer marketed and was not a commercial success, it led the way to subsequent gene therapies that are treating diseases including cancer, inherited retinal dystrophies, and spinal muscular atrophy.  Gene therapy has, in a real way, made “the blind see and the lame walk” (Matthew 11:5).

Viral vector gene therapies, as well as other biologics and vaccines, are produced in living cells.  Often these “biological factories” are human cells that were obtained from a living or recently deceased person.  Perhaps the most well-known human cell line, HeLa, was obtained from the cervical cancer cells of Henrietta Lacks in 1951 and is the subject of a book(2) and HBO film.  HeLa is the most used cell line in biotechnology research and, although it is not used in biomanufacturing, other cell lines derived from human tissue are.  A cell line based on human embryonic kidney tissue, HEK293, is “second only to HeLa in the frequency of their use in cell biology”(3) and is used to manufacture marketed drugs including Luxturna and Zolgensma.  HEK293 is used to manufacture the AstraZeneca COVID-19 vaccine and PER.C6, a cell line based on human embryonic retina tissue, is used to manufacture the Johnson and Johnson COVID-19 vaccine(4).  Use of human-derived cell lines have provided great benefit to patients and are an essential part of pharmaceutical development and production.

It is ironic that the Bible claims Jesus’ ability to make the blind see and the lame walk is through divine power while biotechnology’s ability to do the same by using cell lines such as HEK293 and PER.C6 rests on immoral acts:  these cell lines were obtained from electively aborted fetuses.(5)  Although these cells were procured more than 30 years ago, the general practice of harvesting tissues and cells from aborted fetuses continues unabated. Aborted fetal cells are routinely used from early discovery research to manufacturing, and many experiments require “fresh” cells, ensuring the practice will continue.  Decisions on what cell lines to use are often based upon performance, economics, or simple convenience, without regard to their source or the consequences of their use.

The use of aborted fetal tissue in biotechnology research and manufacturing raises significant ethical concerns for many people.  All involved in the lifecycle of biotechnology development—researchers conducting early experiments, physicians leading clinical trials, employees involved in manufacturing, selling, and distribution, and ultimately patients and consumers—are forced to make decisions that may conflict with their strongly held moral beliefs.  Recently the United States Conference of Catholic Bishops (USCCB) advised the nation’s 70 million Catholics to choose the Moderna or Pfizer/BioNTech COVID-19 vaccine over the AstraZeneca and Janssen vaccines based on the use of aborted fetal cells to manufacture the latter(6).  Unless this situation is addressed ethically compromised products will continue to present a moral dilemma and cause grave concerns.

When faced with moral issues there are many approaches one can take to effect change.  Organizations like the Susan B. Anthony List and their research and education arm, the Charlotte Lozier Institute, seek to effect change through the political process and education.  Citizens can make their voices heard by voting, lobbying politicians, making purchasing decisions based on their moral beliefs, and informing companies and other organizations of their concerns.  The freedom we enjoy in this country allows us to do such things, and this freedom combined with the most successful economic system in history, market-based capitalism, enables entrepreneurs to start companies for any reason they desire.  The existence of all companies depends on their ability to provide goods and services people want, but the reasons companies are created are as varied as the individuals who create them.

Individuals who are passionate about an issue and are fortunate to have freedom and resources must act.  They must decide the best course of action based on the context of their lives, their experience, and their talents.  Creating a company whose products and services can impact an issue and address an immoral situation is one of the best ways to channel this passion.  Those who are passionate about climate change can start a windmill company and use their engineering prowess to create alternatives to fossil fuels.  We have decided to take our knowledge of biotechnology and our experience creating and growing companies and form Agathos Biologics.  Agathos’ existence will depend on the same thing all companies’ existence depends—providing goods and services people want.  The products and services we choose to provide will include those that address the use of aborted fetal tissue in two ways:  by not using it in our research, development, and manufacturing and by creating products that will replace cells derived from it with technically superior, morally acceptable options.

Corporate Strategy

We believe the success of Agathos depends on a clear, coherent, and focused corporate strategy.  We respect those who address issues through political processes, education, and influence, and may participate in such endeavors personally; however, this is not the path that Agathos is pursuing.  Our management team and employees have a limited amount of time and energy, and we will remain disciplined in how we use these resources.  The strategy and day-to-day operations of Agathos will be focused on developing products and services and the company will not spend its resources on any political issues.  We will eliminate such distractions because we believe it is good for business.  The shared goal of the Agathos team will be doing good science to create products and services people want and all who seek this goal are potential members of the team.  As founders, we will be transparent about our motives for creating Agathos, and we recognize that others may not share these motives or agree with our positions.  We have no political litmus test for any employee, consultant, collaborator, or anyone who wants to be part of the Agathos team.  Hiring and partnering with the most talented individuals without enforcing allegiance to a political position or creed allows us to establish a diverse, inclusive, and world-class organization.  We welcome all who want to work within our corporate strategy and ethical commitment and do good science that positively impacts the world.

Agathos’ disciplined strategy will focus on innovation and creation.  There are those who are passionate about the use of aborted fetal tissue and are zealous in their desire to end the practice.  This leads them to spend time and energy arguing that products manufactured with these cells are unsafe or lack efficacy.  Unfortunately, in many cases the data are suspect, and this negatively impacts their credibility and others.  Even if the data are compelling, their politics will always subject them to claims of bias and lack of objectivity.  We recognize that cell lines obtained from aborted fetal tissue (AFT cells) have produced products that are safe, efficacious, and saved lives.  Their use in research and development has contributed to many products that we take for granted and have improved human health.  We will not waste time debating these facts.  We cannot put the genie back into the bottle—the best way to address the problem is with a better genie.  Agathos’ strategy, the same as any company, to make better products, is clear and uncontroversial.  Even those who have no ethical concerns recognize it is better from a pure business perspective to remove reasons for consumers not to purchase your product.  And if consumers are presented with a better product—however they define “better”—their choice is also clear and uncontroversial.

Agathos will face the various ethical dilemmas that all companies face with the addition of decisions related to ethical biotechnology development.  If one’s goal is to show one thing performs better than another thing, the logical experiment is a controlled one in which those two things are compared by subjecting them to identical circumstances and measuring their performance.  The most clear and convincing data to show that a cell line performs better than another cell line would be generated by conducting the exact same experiments under as similar conditions as possible, ideally with the same equipment, laboratory, technicians, etc., even blinded where possible.  If our goal is to replace AFT cells, and the most convincing data would be from a head-to-head comparison of the potential replacement with the AFT cells, should we use AFT cells for these experiments?  Is it morally acceptable to use the AFT cells if our goal is to replace them?  This is a difficult decision, but we believe that it is.  We will only use AFT cells in this limited way and will not use them in any other program as a general-purpose cell line.  We recognize that others may not agree with this approach, but we believe only by generating the highest quality data possible will we be able to show we have created a better product.  Additionally, if we did not do such experiments and published our data without the comparison, potential users of the product would invariably conduct head-to-head experiments anyway.

We realize there are those who will be critical of our approach from multiple angles.  AFT cells have demonstrated utility in research and manufacturing and those who see no ethical issues would argue that the largest financial return and impact to patients would be achieved by improving them.  This is a logical strategy, but it is not ours, because we cannot ignore the ethical issues.  Another criticism is that immortalized cell lines established years ago do not require any more abortions beyond the one used to create them, and research and development that requires an ongoing supply of AFT cells is a graver moral issue.  Where opportunities exist for us to reduce or eliminate such practices we would certainly do so, but our experience and expertise in cell and gene therapy puts us in a unique position to address this issue.  Given the widespread use of HEK 293, PER.C6, and other AFT cells, this is still a significant concern.  As others have noted, “one must [avoid] fostering a social climate of approval that would perpetuate the abuses and the injustices.”(7)

The Mission

Agathos will pursue therapeutic products and use the cell lines we develop in our own research and manufacturing in addition to providing them to others.  The tremendous growth and investment in regenerative medicine, which continues at a record-breaking pace(8), provides opportunities we want to pursue to positively impact patients with unmet medical needs.  This approach will allow us to demonstrate the utility of cell lines we develop and provide an example and blueprint for ethical biotechnology product development.  As an industry we must do better providing products and services that consumers want, and this includes those they can use with a clear conscience.  Agathos will lead these efforts and looks forward to working with individuals and organizations that share our vision.

 

1. Human Genome Project FAQ. National Human Genome Institute web site https://www.genome.gov/human-genome-project/Completion-FAQ (2020).  Accessed April 16, 2021.

2. Skloot, R. The Immortal Life of Henrietta Lacks. (Crown/Random House, 2010).

3. Lin, Y.-C. et al. Genome dynamics of the human embryonic kidney 293 lineage in response to cell biology manipulations. Nat Commun 5, 4767 (2014).

4. Prentice, D. & Sander Lee, T. What you need to know about the COVID-19 vaccines. Charlotte Lozier Institute web site https://lozierinstitute.org/what-you-need-to-know-about-the-covid-19-vaccine/ (2021).  Accessed April 16, 2021.

5. US-FDA Meeting Transcript, FDA-CBER Vaccines and Related Biological Products Advisory Committee Transcript May 16, 2001. Wayback Archive of FDA web page https://wayback.archive-it.org/7993/20180125210145/https://www.fda.gov/ohrms/dockets/ac/01/transcripts/3750t1_01.pdf (2001).  Accessed April 16, 2021.

6. Answers to Key Ethical Questions About COVID-19 Vaccines.pdf. https://www.usccb.org/resources/Answers%20to%20Key%20Ethical%20Questions%20About%20COVID-19%20Vaccines.pdf (2021).  Accessed April 16, 2021.

7. Luño, V. Rev. A. R. Ethical Reflections on Vaccines Using Cells from Aborted Fetuses. National Cathol Bioeth Q 6, 453–459 (2006).

8. 2020: Growth and Resilience in Regenerative Medicine. http://alliancerm.org/wp-content/uploads/2021/03/ARM_AR2020_FINAL-PDF.pdf (2021).  Accessed April 16, 2021.