(I) Homage to Dr. Clodomiro Picado. 45th years of the Clodomiro Picado Institute.

Here I would like to translate a video, the original in spanish on the:

45th years of the "Instituto Clodomiro Picado" 

Costa Rica

I do have some preferences, and this is one. To me this is one example of science, social involvement and dedication. 

Dr. Clodomiro Picado Twight was a humanist pioneer, not only toxinologist. He promote regulations to prevent snakebite deaths between the poor peasants of Costa Rica that 100 years later are still innovative and challenging. 
English is not my first language so please, take the good intention and I apologize before hand for all the mistakes. Thank you. 

This is an interview to Dr. José Mª Gutiérrez, in 2015  for a Costa Rica TV program called "ConCiencia". Very good play on words, that translated a part would be "With Science" and together becomes "Consciousness". 

1st PART

P: Hello, how are you? welcome to ConCiencia, today we have the pleasant visit of Dr. Jose Mª Gutiérrez Gutiérrez, who is an investigator at the Clodomiro Picado Institute, University of Costa Rica, and professor at the Faculty of Microbiology, at the University of Costa Rica.

Dr. Jose Mª Gutierrez at ConCiencia TV 

https://www.youtube.com/watch?v=f4GQYZKVFkc

P: “Chema”, as affectionately we know you, welcome to our program.

DrJMG: Thank you so much. It is a pleasure to be here.

P: We are going to talk about the 45 years of the Clodomiro Picado Institute, founded in 1970. Please, tell us the historic sequence on how the Institute was founded in those times.

DrJMG: Yes, in fact, the Clodomiro Picado Institute is the corollary of a long term national project, that we could say starts with the pioneer work of Clodomiro Picado Twigt, who worked on the decade of 1910, 20 and 30, he died in 1944, and between the many topics that Cloromiro Picado investigated, studied, are the snakebites. He was worried for this problem that affects mainly the farmers of our country, the agriculture workers and…

P: Mainly the banana workers on those times…

DrJMG: Yes, and laborers in general, fincas, small farmers etc. As he saw that these people arrived to the hospital almost to die only in there as a result of a snake bite and that the country did not had an answer against it, then he devoted himself to scientifically study the problem and not only he study it but tried hard to found solutions for it. 

He realized that Brazil manufactured snake anti-venom serum since 1901, at the Butantan Institute, and then he reach an agreement with the Butantan Institute to import antivenom from Brazil to be used in Costa Rica. Furthermore, Clodomiro Picado brought snakebite issue at political levels because he promoted, together with the Heath Minister of the time, Dr. Solon Nuñez Frutos, a very pioneer law in the continent called "Law of defense against "Ofidismo"" that established several regulations with the aim that those peasants would have access to the anti-ophidic serum (snake anti-venom) 

*The word "ofidio" comes from the greec ὀφίδιον, diminutive of ὄφις, snake. 

Ofidismo would be the term used to define a snakebite. This term, is widely used is South America. In Spain the word "serpiente" is more common.

Serpiente comes from the latin "serpens", literally. It has an indoeuropean root as for example in hindi, the word used for snake is "sarpa". 

P: and this law is established…

DrJMG: In 1926…

P: and this law obliges the Government to…

Dr. Clodomiro Picado Twig

DrJMG: obliges the Government to have anti-venom, obliges for example the railroad drivers to transport the snakebitten people to the cities where there were hospitals and very interesting, obliges the farm owners to have anti-venom in the farm, and in the case a farm owner did not had the anti-venom and a laborer died from snakebite, the farm owner had to pay for two years the salary of this person to the family. So, really, Clodomiro moved in a very a wide range,  from basic science to the application of the knowledge with the snake anti-venoms up to the intervention into the political scope for the resolution on the problem. 

Now, Cloromiro Picado dies in 1944 leaving behind his tradition, with his followers like Alfonso Trejos Willis, Nanbadilla, Luis Bolaños and other people.  On the sixties, there is a resurgence of this topic in our country because the political sectors that prompted the reform of health sector wanted to wide the range of health services as part of the political movement. They where interested and thought that it was time for the country to have their own production of snake anti-venom, then, it happened a very particular conjuncture with the coalescence of the Costa Rica University, initially trough Dr. Jesús Mª Jiménez Porras, that was Biochemistry professor of the Medicine School, and later on Dr. Róger Bolaños that was the central figure in all this project, with the political support of the Health Ministry…

P: Róger Bolaños from the Microbiology Faculty… the Faculty was already existing as such…

Left: Dr. Clodomiro Picado Twight holding a snake.
Right: Dr. Róger Bolaños

DrJMG: Exactly, the Faculty was created in 1956 and Róger Bolaños was the Professor of Immunology of the Faculty of Microbiology and they come to him which, let it be added, was the son of Luis Bolaños, disciple of Clodomiro Picado so, there is a direct lineage that brings Róger Bolaños. It was also very important at that time the political will, isn’t it? And in this case this was reflected on the will of the Ministry of Health, Dr. Alvaro Aguilar Peralta, that clearly saw the situation and gave a decisive political support and a third component in this synergy was the presence of a North American military veterinary doctor that was working in the USA Embassy, Dr. Herschell Flowers, who had experience with snakes and snake anti-venom in USA and was very motivated for this project, with the support of the USA Embassy.

So, Flowers together with Róger Bolaños and the political support of Dr. Aguilar Peralta… it was like a conjunction, the celestial bodies aligned, and this program was firmly supported. The program initially was called “Program of Snake Anti-venoms” and belonged to the Health Ministry. As a result of their work, at the beginning of 1967 the first batches of anti-venom: the poly-specific anti-venom against vipers and the anti-coral anti-venom were released. 

Polyvalent anti-venom still manufactured nowadays

From 1968 Róger Bolaños was the director of that Program. The Program was so successful, the anti-venoms started to be used on the country with a lot of success, clinically were much better than the imported anti-venoms, so the Health Ministry decided to transform the Program into an Institute and financed both by the Costa Rica government as well as by A.I.D. (Agency for International Development) of the USA, the first plants were built of what is now 

The anti-coral antivenom of the Institute

the Instituto Clodomiro Picado, on a land belonging to the Ministry of Health, in “Dulce Nombre de Coronado”. This was in 1970, in April 1970 the “Instituto” was inaugurated, then belonging to the Ministry of Health. In 1970 the Government changes, Dr. Aguilar Peralta participated on the foundation of the “Instituto” but then next minister is Dr. José Luis Orlich Bolmarsich on the Government of Mr. José Figueres Ferrer. On those years, Dr. Bolaños and the managers of the University take an important step, tremendously lucid, that was to promote thorough an agreement between the University and the Ministry of Health, that the Program would become part of the Costa Rica University. This took place in 1972. The most important is that becoming part of the University of Costa Rica, the “Instituto” assumes the academic and humanistic philosophy of the University of Costa Rica as the driving motor for its development, and this implies that the project is not only dedicated to manufacture the anti-venoms, as it was the original goal and as happen in many centers in South America for example, but that added to the production, there will be university activities of education, research and social involvement and it is precisely these “integrality” that when it is time to approach a complex health topic with many elements and components, what gives the strength and enthusiasm that allowed the “Instituto” to strongly develop on the decades that followed.

For further information you can refer to the article (Editorial):

Toxicon, Volume 54, Issue 7, 1 December 2009

Special Issue: Bothrops asper, 

From natural history to public health

Bothrops asper: Beauty and peril in the Neotropics, 
Editorial. pg 901 - 903
José Mª Gutiérrez. Instituto Clodomiro Picado. Facultad de Microbiología. Universidad de Costa Rica.
http://dx.doi.org/10.1016/j.toxicon.2009.06.012

Snakes have inspired fascination and fear to humans since ancient times, as reflected by the common presence of these reptiles in the mythology of many civilizations. Such sense of awe has been associated to the impact that snakebite envenomation has had worldwide, to the amazing life patterns and adaptations of these reptiles and, more recently, to the exciting discoveries that science has provided on their natural history and on the chemical composition and toxic effects of their venoms and isolated toxins. Moreover, progress in the knowledge of the structural and functional properties of venom components has paved the way for the use of these complex mixtures as sources of lead compounds for the development of diagnostic and therapeutic agents.

There are many species of venomous snakes, classified in the families Colubridae (sensu lato), Atractaspididae, Elapidae and Viperidae. A small group of them are responsible for most cases of human envenomations. Examples are the cobras, kraits and some viperids in Asia, the saw-scaled viper in the sub-Saharan Africa, rattlesnakes in North America, and some species of lance-head vipers in Central and South America. Among them, Bothrops asper inflicts the highest toll of envenomations in southern Mexico, Central America and northern regions of South America ( Gutiérrez, 1995 and Warrell, 2004). It is estimated that, in Central American countries, B. asper is responsible for more than 50% of the total number of cases, and for almost all fatalities due to snakebite envenomation ( Bolaños, 1982 and Gutiérrez, 1995). The impact of B. asper in public health and other aspects of life in this region has been well known since the times of precolumbian cultures, one of which named this species ‘Bec-Kara-Acá’, the ‘devil that brings death when it bites’ ( Picado, 1931).

A large amount of work has been performed on the biology and toxinology of this species. The pioneer in the study of B. asper and other Central American snakes was the renowned Costa Rican scientist Clodomiro Picado (1887–1944) who, after his advanced studies in France, developed a fruitful career in the clinical laboratory of San Juan de Dios Hospital, in Costa Rica ( Gutiérrez, 1986). Among his many areas of interest, the study of snakes, their venoms, the clinical features of envenomations, and the development of treatments occupied a leading place in his research agenda. His efforts resulted in many scientific publications and were summarized in the book Serpientes Venenosas de Costa Rica. Sus Venenos. Seroterapia Antiofídica ( Picado, 1931), which covers his studies of many years. Picado promoted the introduction of serotherapy, i.e. the use of antivenoms, in the treatment of snakebite envenomation in Costa Rica, through cooperation with Instituto Butantan (Brazil), which provided the antivenoms that were successfully used in Costa Rica for several decades (Picado, 1931).

Clodomiro Picado (1887–1944) holding an adult specimen 

of Bothrops asper close to his laboratory at Hospital 

San Juan de Dios, San José, Costa Rica (circa 1930).

In the 1960s, Jesús María Jiménez-Porras, a professor of Biochemistry at the School of Medicine, University of Costa Rica, performed innovative research in the biochemical characterization of snake venoms, including B. asper, then classified as B. atrox ( Jiménez-Porras, 1964). He unveiled a pattern of geographic and individual variation in the venom of this species. 

Then, an outstanding inter-institutional effort to confront the problem of snakebite envenomation in Costa Rica was promoted, with the participation of the Ministry of Health, the University of Costa Rica and the Embassy of the United States of America (Gutiérrez and Rojas, 1999). Thanks to this joint venture, known as Programa de Sueros Antiofídicos, Costa Rica succeeded in producing the first batches of antivenoms in Central America, and has since been self-sufficient in the supply of these immunobiologicals. In 1970, the Instituto Clodomiro Picado emerged from this program under the leadership of Róger Bolaños, a brilliant scientist and a dynamic technological entrepreneur who contributed to the study of snake venoms and consolidated the production of antivenoms in Costa Rica ( Bolaños, 1984). Many projects carried out at this institute, together with the work performed by researchers in other laboratories and countries, have generated a large body of knowledge on B. asper, its natural history, its venom and its impact in public health.Owing to the abundance of scientific literature on this species and to the fact that it is often dispersed in diverse sources, some of which are not easily accessible, it is difficult to have a comprehensive view of the available knowledge on this ecologically and medically relevant viperid. Moreover, the ever growing trend towards specialization in the study of snakes and venoms has brought a body of novel findings that creates the need of integration of such widespread knowledge. 

The aim of this special issue of Toxicon is to bring together, in a single publication, the available information on B. asper, on its natural history and intraspecies variation, on the biochemistry and proteomics of its venom, on the pathological and pathophysiological effects that B. asper venom induces at the experimental level, on the clinical features of human envenomations and their treatment, and on the search for novel therapeutic tools that could improve the management of these envenomations in the future. Mahmood Sasa, Dennis K. Wasko and William W. Lamar present an overview of the natural history of B. asper. Besides published data, they include unpublished observations by field herpetologists on the fascinating adaptations and life patterns of this species. Mónica Saldarriaga-Córdoba and colleagues investigate various factors influencing the variations in phenotypic parameters of B. asper, presenting valuable clues for interpreting intraspecies variability.

Yamileth Angulo and Bruno Lomonte review the proteins that have been isolated and characterized from the venom of B. asper, describing their structural features and their toxicological profile. Alberto Alape-Girón and colleagues provide a detailed review of the proteomics of B. asper venom, highlighting the complexity of its geographic and ontogenetic variation, and several implications of such variability. José María Gutiérrez and colleagues summarize the experimental studies on the local and systemic pathology and pathophysiology of envenomations by B. asper, reviewing the mechanisms of venom-induced tissue damage and the ensuing processes of tissue repair and regeneration. In addition, Catarina Teixeira et al. discuss the multifactorial inflammatory response elicited by B. asper venom.

Rafael Otero presents an overview of the complex and often severe clinical manifestations of envenomation by B. asper, as well as on the therapy of B. asper snakebite cases in South and Central America. Finally, Bruno Lomonte and colleagues review the studies on the search for inhibitors that could neutralize the toxic activities of B. asper venom, including antibodies, natural inhibitors and synthetic molecules. Their work highlights the potential usefulness of inhibitors for the improvement of the therapy of envenomations, especially concerning the halting of the progression of local tissue damage.

The collection of works included in this special issue offers a comprehensive view of the available knowledge on this venomous species. It also evidences gaps in our understanding of B. asper, and highlights the need to perform additional studies on subjects that range from natural history and venom composition and effects, to the public health and ecological impact of this species. A central goal of this issue is to promote a productive dialogue between toxinologists and specialists working on natural history and on the clinical aspects of envenomation. The detailed account of many aspects of the natural history of B. asper presents a number of intriguing questions on the adaptive role of venom. Likewise, the complex clinical alterations described in human envenomations by this species demand a deeper understanding on the mechanism of action of venom components, and on the possible synergistic effects of various toxins.

It is hoped that the integrative effort presented in this issue will foster the interest of scientists, technologists, public health workers and students in pursuing the study of unknown aspects and enigmas that remain open for understanding B. asper and related snakes. The gathering, in a single issue and for a single species, of scientists working in fields as diverse as herpetology, evolutionary biology, biochemistry, pharmacology, experimental pathology, immunology, clinical medicine and epidemiology, has been a highly stimulating and rewarding experience.

I deeply thank Alan Harvey and the editorial staff of Toxicon for supporting in many ways the publication of this issue. I am especially grateful as well to the authors who agreed to participate in this effort, and to the reviewers who, through their criticisms and suggestions, contributed to the improvement of the manuscripts and to the completion of this project. This special issue of Toxicon is dedicated to the memory of Clodomiro Picado and Róger Bolaños, pioneers of Toxinology and of the study of B. asper in Central America.

ॐ लोकाः समस्ताः सुखिनो भवन्तु ॥

Om Lokah Samasthah Sukhino Bhavantu

May all beings everywhere be happy and peaceful.