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Horses as a Material Asset in Antivenom Production: What is Their Limit?

Historically, horses have been manipulated as ‘soulless machines’ whose useful characteristics may be expanded. In 1833, the Journal of the Franklin Institute described the expression ‘horse power’ as technically applicable “to any apparatus by means of which a horse is made to exert his power in propelling machinery.” In the late 19th century, a new use emerged and equine bodies were subjected to scientific appropriation as a material asset for modern immunology. Since then, equine blood has functioned as an essential raw material in the antivenom industry. Even so, or for this very reason, just as horses have been trapped in a nest of vampires, their dramatic and unequivocal contribution as blood suppliers has been left to oblivion. Equine use in the serotherapy industry remains the horse’s most disregarded role, a systematic exploitation of animal bodies and suffering that has been carefully erased from history. Today, the absence of specific criteria to detect equine injuries resulting from continuous injections of venoms and subsequent bloodletting continues to be a major problem in the antivenom industry. What are the limits of a horse’s body? The answer to this question contributes to discussion on the connections between ethics, human-equine interactions and experimental techniques by examining antivenom production in Brazil, as well as related international challenges. With no intentions of exhausting the topic, this paper presents considerations that justify a greater commitment to the fate of horses serving the antivenom industry.

The Invisible Source of Raw Material

For 130 years, the conditions that serum-producing horses face has been a systematically neglected topic. These animals have been subjected to repetitive use in scientific experimentation, without adequate guidelines for managing the multiple impacts that the hyperimmunisation process has on their bodies. Although some improvements have been made, the current method of using horses to produce plasma follows the traditional model for producing anti-diphtheria serum, initiated in Europe in 1894.

 It consists of successive injections of toxins with adjuvants followed by bleeding to obtain hyperimmunised plasma for the production of antivenins, anti-rabies, antibotulism, and antitetanus serums. It was not until 2016 that the World Health Organisation Guidelines for the Production, Control and Regulation of Snake Venom Immunoglobulins recommended that the antivenom industry adopt ethical practices regarding the animals it uses. According to WHO Guidelines, monitoring of animals used to produce antivenom must include postmortem examination, necropsy and histopathology, allowing a careful analysis of causes of death which must, in turn, be made available for external review.

This commitment to transparency regarding the condition of seroproducing horses has not been assumed by the antivenom industry. Until now, animal welfare directives for horses used in the industrial production of hyperimmunised plasma have not established specific guidelines regarding production procedures. When they do exist, such guidelines are defined by the industry itself, comprising an obvious conflict of interests. Official standards regarding the limit of blood that can be extracted, frequency of collection, and criteria to be observed to define when an individual should be removed from the program have not yet been established.

The broad impact of this lack of official standards are quite significant. In 2021, according to the Research and Market report, the global antivenom market was valued at USD 1.08 billion in 2023 and is anticipated to project impressive growth in the forecast period, and is expected to reach USD 1,585.01 billion, in 2026. In such a workplace, millions of horses and other equids have been used as a source of raw material for serum as well as in experimental activities. This data does not cover other types of equine serum, such as anti-rabies, anti-diphtheria, anti-botulism, and anti-tetanus varieties. Neglecting to monitor the condition of horses used to produce antivenom is a silent ingredient of endemic crises involving snakebite. Since 2017, the World Health Organisation has added the latter to its list of neglected tropical diseases, mainly affecting rural populations in Africa, Asia and Latin America. The highly complex and inefficient production system of the worldwide antivenom industry remains a current challenge mostly within the poor countries of these regions.

In Brazil, the equine serum industry faces a series of problems that have not been resolved over the last 130 years. In 2016, the Ministry of Health issued a not explaining that the distribution situation of anti-rabies and anti-venom serums had been faulty “due to constant rescheduling of deliveries caused by workers’ strikes, theft of animals, and problems in the supply of raw materials”.

It is worth highlighting that Brazilian hyperimmune serum was first subjected to specific regulation in 2017, through Resolution 187. The resolution, approved by the National Health Surveillance Agency, aims to guarantee the quality, safety and effectiveness of antivenoms and other equine serums. Since its implementation, the production of antivenoms has been suspended by three of the four public producers of horse serum. Currently, only the Butantã Institute continues to supply the public health system, significantly compromising the national supply of antivenoms and other sera. According to the aforementioned Resolution, registering a new hyperimmune serum requires a technical report with specifications on the side effects, adverse reactions, restrictions or precautions to be considered, as well as precautions and warnings, and product development history including pre-clinical and clinical trials, among others. Specific information must also be included on all stages of manufacturing, including the equine immunisation plan and the site where the source material or toxin injections, bleeding procedures, and rest period will take place.