The University of Southampton

Author: Lily Waldram

Navigating the Ethical Concerns Surrounding Foetal Bovine Serum

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The concept for my summative blog emerged during my dissertation lab project, where I used HepG2 cells to assess the hepatoprotective impacts of chlorogenic acid against paracetamol induced liver toxicity. During this process I became familiar with cell culture, treating and assaying them most days, but when I came to seed the cells myself and prepare new culture medium, my attention was brought to foetal bovine serum. When researching the topic I found interest in the ethical debate surrounding the production of foetal bovine serum and the demand for alternatives.

Foetal bovine serum (FBS) is a key component of cell culture medium and is used extensively for research applications. It contains essential hormones and growth factors providing a rich culture system; supporting the widest range of cell types, including cell lines and primary cells.

Figure 1: European Serum Products Association Summary of FBS Production.

Although figure 1 provides a thorough overview of the FBS production process, it fails to describe the actual harvest, the point of most concern. FBS is typically obtained by the cardiac puncture of cow foetuses sourced from cows found to be pregnant after slaughter. This is carried out once the foetuses are declared deceased and without the administration of anaesthesia.

An article from 2002 covers the proposed reasons behind the ethical concerns surrounding FBS production and the potential for foetuses to experience pain during the process. One of the primary ethical concerns regarding the harvesting procedure involves the resistance of mammal foetuses to anoxia; the complete loss of oxygen supply to the body or brain. Mammals possess protective mechanisms allowing maintained brain function even after oxygen deprivation. These mechanisms include the ability to meet energy requirements via anaerobic respiration, the prioritisation of blood flow to critical organs such as the brain, and a reduced oxygen demand in the foetal brain, compared to adults. It is expected that the bovine foetuses have normal brain function at time of cardiac puncture, allowing us to assume that they are aware of the procedure and experience pain as a result. The paper then goes on to explore the timeline by which the cow foetus develops nociception and the ability to experience pain.

Since this paper is now over 20 years old I looked for more recent advancements. This led me to an article addressing the animal welfare ethics concerning FBS production and how the industry has altered it’s practises to avoid such concerns.

To summarise, the article discusses the debates regarding foetal sentience and consciousness, raising concerns about potential suffering during the procedure and proposes steps to minimise harm. They specifically make reference to the European Food Standards Agency (EFSA) recommendation to immediately open the uterus, stun and kill the foetus upon detecting pregnancy in a slaughtered cow. This ensures the foetus is unconscious and therefore doesn’t experience pain during the blood extraction. They suggest increased monitoring within the serum industry to ensure compliance with ethical standards and that by implementing such measures, the industry can demonstrate its commitment to ethical practise. Like the 2002 paper, they also conclude that it is time for researchers to adopt more modern approaches to human cell culture-based research and to move away from the use of FBS.

Figure 2: Summary of Emerging Alternatives to FBS

To conclude, at present time the production of FBS is deemed to be up to ethical standards providing individual producers follow legislation and guidelines provided. It’s clear that to fully address the concerns around animal welfare, alternatives to FBS are required. By adopting such alternatives, we can achieve greater scientific accuracy whilst demonstrating stronger ethical consideration.

References:

Jochems, C.E.A., van der Valk, J.B.F., Stafleu, F.R. and Baumans, V. (2002). The use of fetal bovine serum: ethical or scientific problem? Alternatives to laboratory animals : ATLA, [online] 30(2), pp.219–27. doi:https://doi.org/10.1177/026119290203000208.

McCann, T.J. and Treasure, C. (2022b). Addressing Animal Welfare Issues in Fetal Blood Collection for Fetal Bovine Serum Production. Alternatives to Laboratory Animals, 50(5), pp.365–368. doi:https://doi.org/10.1177/02611929221117992.

The Scientific Misconduct of Paolo Macchiarini

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I found interest in the Paolo Macchiarini case, when watching ‘Bad Surgeon: Love Under the Knife’ on Netflix, described as one of the biggest frauds in modern medical history. As a biomedical sciences student and a fan of true crime documentaries I inevitably binge watched the series. Then when I attended lectures on tissue engineering and the ethics and laws surrounding the use of body parts in biomedical research, I decided to produce this blog combining what I’d learnt.

Paolo Macchiarini is an Italian born thoracic surgeon and researcher in regenerative medicine. He rose to fame in 2008, when he successfully completed a thoracic transplant in Barcelona by chemically stripping a donor windpipe and then seeding the bare scaffold with stem cells from the patient’s bone marrow (autogenic cells). (1) After his initial success Macchiarini was recruited by the Karolinska Institutet (KI) as a visiting professor and researcher in regenerative medicine and stem cell biology as well as being employed by the Karolinska University Hospital as a consultant and surgeon. Here he begins to use synthetic plastic windpipes and patient stem cells. Out of the eight thoracic transplants he performs at both Karolinska and in Russia, seven of them die within a few months or years post-op.

Above: Timeline depicting the series of events.

When reading around the ethics of regenerative medicine specifically, I found this article discussing the main ethical considerations concerned, including: patient consent, safety and efficacy, professional responsibility and, equity and fairness.

During this time, Macchiarini failed to consider any of these factors.

It was found that a proper risk assessment was never performed nor did his team seek permission from the government for the use of the plastic scaffolds, stem cells or chemical growth factors required for the procedure. Furthermore, Macchiarini was found to deliberately misrepresent his results in publications. Some papers claimed improvement in patients, however there was no record of examination. The plot further thickens when the validity of the murine studies was assessed. In the critical rat-model papers, the data collected, weight-gain data and computed-tomography (CT) overexaggerated the success of the study. (2) So where usually years of thorough pre-clinical testing is conducted to ensure the windpipe is fit for use, Macchiarini essentially publishes made up results to bypass this stage.

What I found to be especially concerning was that the misconduct was not limited to Macchiarini, but actually extends to his fellow researchers, his supervisors and the Karolinska Institutet itself. In order to carry out the transplantation, permission from the Swedish Medical Products Agency (MPA) is required due to the fact that synthetic tracheas are classed as “advanced therapy medicinal product”. Who was at fault was never clarified. Additionally, the Karolinska Hospital had deemed the operations as care interventions on the basis of so-called vital indication, (last resort treatment), but when reassessed it was found that some of the patients were actually relatively healthy, making the risk of the surgery completely unjustifiable.

Above: Video Summarising the Case

After the thorough investigation of the Karolinska Institutet, an action plan was put in place to prevent future incidents. To summarise, the main initiatives include but are not limited to; strengthened ethical orientation, increased support for leaders, establishment of the council for the investigation of deviations from good research practise, review of admissions and recruitment and support systems put in place to aid incident reports. (3)

This case encapsulates the importance of ethical research and the risks associated with regenerative medicine, and is a lesson to scientists about our responsibility in producing genuine data.

Extra Thumbs

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Could having an extra set of thumbs boost our capabilities as humans?

While browsing the web, I stumbled across an article discussing and assessing the potential benefits of manufacturing and utilising extra limbs to help the public with work and home life. We already know the benefits of replacing previously lost body parts, but is it possible that adding additional limbs to typically functioning limbs could make humans more efficient. Could it be that waiters could carry more plates with an extra thumb, could a builder lay more bricks with an extra arm, could we run faster with an extra leg?

Instead of replacing limbs, scientists are looking at augmenting the remaining functioning limb.

When thinking about how an extra limb could improve the efficiency could improve my own life, the opportunities seem endless, as a biomedical science student, an thumb could mean that holding double the test tubes.