CLiR No. 3 - Human beings, Ethics, and Clinical Research

ART & LITERATURE

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YEAR ONE

NOV-DEC

3 MESSAGE FROM THE DIRECTOR 4EDITORIAL 6 DISCOVERERS OF CRISPR/CAS GENETIC EDITING WIN NOBEL PRIZE IN CHEMISTRY 7 NEW FRONT-END NUTRITION LABELLING GOES INTO EFFECT IN MEXICO 8 AFRICA ERADICATES POLIO AFTER TWENTY-FOUR YEARS, WITH NO REPORTED CASES 10 TTATTOO INK FOR CANCER DETECTION 12 DRUGS TO PROMOTE ORGAN SURVIVAL IN ELDERLY DONORS

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18 ON ETHICS AND CLINICAL RESEARCH 22 THE SCOPE AND RELEVANCE OF CLINICAL RESEARCH

48 BIOETHICAL AND HUMAN RIGHTS CONSIDERATIONS IN THE SELECTION PROCESS FOR HEALTH CARE FOR PATIENTS WITH COVID-19

25 WHERE DRUGS AND MEDICINES COME FROM; A BRIEF ACCOUNT OF THE DEVELOPMENT OF PHARMACEUTICALS

51 SCIENTIFIC ETHICS AS SEEN IN LITERATURE

32 MEDICAL ETHICS AT THE PRESENT TIME

55 THE ORIGINS OF QUANTUM PHYSICS

35 MEXICAN RESEARCHERS DISCOVER THAT BLACK PEPPER MAY HAVE ANTI-VIRAL EFFECTS AGAINST COVID-19 38 THE HEROES OF CLINICAL RESEARCH

14 FEASIBILITY OF USING DEEP LEARNING TO DETECT CORONARY ARTERY DISEASE

42 HUMAN BEINGS, ETHICS, AND

16 AT THE END OF THE CHAIN THERE ARE REAL PEOPLE

46 THE PATIENTS HAVE IT RIGHT

CLINICAL RESEARCH

ART & LITERATURE

CONTENT

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53 LÓPEZ-GATELL AND BIOETHICS IN THE TIME OF THE PANDEMIC

57 THE SMART DECADE 60 EDITION INQUIRY 61 THE AUTHOR AS ANTHROPOLOGIST 65 CLIR TOON

S TA F F DIRECTORY

•DIRECTION GENERAL DIRECTOR Marco A. Cid

• T R A N S L AT O R

• C O L L A B O R AT O R S

Gregory J. Dechant

Ca rm en de l a Rocha J ennefer I vet h M e rca do G ui l l erm o Ca l ett i Da nte Al duci n Ana L ui sa Ca ba l l ero El vira Rol dá n M e rca do Federi co L erner T hor Ni sse n Art uro Áva l os Tonat i uh G onzá l ez Pat ri ci a E. Si l va Col unga J ua n Vá zquez M a rt í nez J orge L a urea no Eugeni o El i sa G i l H erná ndez J osé L ui s Rom ero I ba rra M a uro Orozco J a cquel i ne Ang ui a no Orí ge nes Rom ero Bruno M ung uí a F ra nci sco He rná ndez Ri ck Rui z-Da na

• GRAPHIC DESIGN

EX EC U TI VE D I R EC TO R

Ivette Venegas

César A. Pérez Valencia

•EDITORIAL EDITOR IN CHIEF

•COMMERCIAL

Carolina Villanueva

• STYLE CORRECTION C A RO L I N A V I L L ANU E VA GR EG O RY J. D EC H ANT

COMMERCIAL DIRECTOR Fabián Villegas COMMERCIAL MANAGER Jorge Castro

ART & LITERATURE

MARKETING Marco A. Limón del Toro Natalia Robles Cabrera

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Clinical Research Insider, year 1, No. 3, november-december 2020 is a trademark of CRPS, Clinical Research Professional Services, LLC. All rights reserved. Clinical Research Insider is a bimonthly publication, published in Calle Volcán Popocatépetl No. 3352, Colli Urbano, Zapopan, Jalisco, C.P. 45070. Tel. 33 20 02 86 97. Website: clirinsider.com. Editor in Chief Carolina Villanueva López, email: carolina.villanueva@cidvid.com.mx. Reservation of Rights to the Exclusive Use: in process. ISSN: pending at the National Copyright Institute. Title and Content Lawsuit: pending. The content of the articles and advertising is the responsibility of their authors and sponsors. Clinical Research Insider is not responsible for the information in the advertising content. Prices shown in this publication are for information purposes only and are subject to change. Printed at Coloristas y Asociados, S.A. de C.V., Jalisco, Mexico. This issue was completed in december 2020 with a print run of 10,000 copies.

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THE YEAR HUMANKIND OVERCAME ILLNESS

Humanity is now waging a war with high hopes of being victorious. Part of this result is due to research into and development of new therapeutic options, from the new vaccines being proposed to medications being developed.

None of this could be carried out without clinical research and studies involving human subjects.

In this issue we examine all of the ethical and scientific aspects of the involvement of human beings as research subjects. Humanity has built up its discoveries through the scientific method, but it is important to remember that human beings must be treated in accordance with three maxims when involved in scientific research: respect for individuality, justice, and the constant effort to work on behalf of their wellbeing. The guild of scientists has taken giant steps in this area, producing various documents that serve as the basic pillars of research with human subjects, including the Nuremberg Code, the Belmont Report, the Declaration of Helsinki, and guides to good clinical practices.

Humanity is at a point of no return, moving toward a universe in which the human being is called to be the center of everything. It is only thus that we shall be able to conquer our microcosm and begin to explore our macrocosm.

Cordially yours.

Marco Cid, Director studied pharmaceutical chemistry at the Universidad La Salle before earning an MBA from the ITESO and a management degree from the IPADE Business School. He is an expert in medical research and development, an entrepreneur, the founder of various non-profit and for-profit enterprises, and the creator of a private capital investment fund.

MESSAGE FROM THE DIRECTOR

We are approaching the end of the year 2020. It is known to all that it was an extraordinary year, defying all logic. Humankind never expected to experience, in its own flesh and blood, a pandemic of this dimension. The beginning was complex and confusing, as we failed to see or understand what was going on: the virus took us all by surprise, and to everyone’s astonishment, we had to step back and protect ourselves.

Little by little we are beginning to see different options, new treatments, possible vaccines, and ways of detecting the illness more quickly and more effectively. Many, however, were unable to pass the test and have lost the battle.

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EDITORIAL Health and Ethics in the Contemporary World “Medicine is the only universal profession, that everywhere follows the same methods, acts with the same goals, and seeks the same ends.”

Sir William Osler

The origins of medical ethics go back to ancient Greece, when Hippocrates drew up a set of ethical duties for healers, offering them what is still to this day known as the Hippocratic Oath.

There followed, in the fifth century CE, the code known as the Formula Comitis Archiatrorum and the first book devoted to the subject of medical ethics, Practical Ethics of the Physician. Thanks to the perseverance, ingenuity, and curiosity of scholars through the ages, the world of research in the health sciences has never ceased to develop and widen its scope. At the present day, there are ethical committees on clinical research around the world, responsible for overseeing the proper development of biomedical research in general.

It is a pleasure for us to collaborate with researchers and health professionals so that this specialized knowledge may reach all levels of society. The issue you hold in your hands contains some surprising and up-to-date news from the health science world, including interviews conducted with some important members of the scientific community: Dr. Ana Luisa Caballero, chairwoman of the ethics committee of iBiomed, and Dr. Juan Vázquez Martínez, a member of the Centro de

Investigación y de Estudios Avanzados of the Instituto Politécnico Nacional (CINVESTAV), who led the research into the properties of black pepper in combating Covid-19, as well as a series of interesting articles and opinion pieces by health specialists in the areas of clinical research, pharmacology, and their connection with medical ethics.

Welcome to issue number 3 of Clinical Research Insider, where you will find a variety of select content on the health sciences, technology, and leisure. Enjoy along with us this treasure of news content prepared especially for those with a passion for science and human knowledge, and expect a further series of fascinating issues in the coming year.

Carolina Villanueva López, EIC Editor and Content Creator

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DISCOVERERS OF CRISPR/CAS GENETIC EDITING WIN NOBEL PRIZE IN CHEMISTRY

LATEST NEWS

On 7 October 2020 the Royal Swedish Academy of Sciences announced the winners of the Nobel Prize in Chemistry: Emmanuelle Charpentier of the Max Planck Institute in Berlin and Jennifer A. Doudna of the University of California, Berkeley, for developing a method for editing the genome.

The CRISPR/Cas9 editing tool works like a pair of genetic scissors designed to change the DNA of organisms with great precision. This system has revolutionized scientific research, making it possible to generate animal and cellular models of genetic diseases and thus to understand their mechanisms in clearer ways. There is also great potential for gene therapy, correcting specific mutations present in diseases that still have no treatment.

The scientists first published their research in August 2012 in an article for the prestigious journal Science, in which they described the efficiency, versatility, and potential of their tool. Eight years after that publication, however, the veritable ramifications of this discovery are still to be seen.

Sources: Real Academia de las Ciencias de Suecia. Press release: The Nobel Prize in Chemistry 2020. THE NOVEL PRIZE. 2020. Jacinto F V, Link W, Ferreira BI. CRISPR/Cas9-mediated genome editing: From basic research to translational medicine. J Cell Mol Med. 2020;24:3766–78.

Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science (80- ). 2012;337(6096):816–21.

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NEW FRONT-END NUTRITION LABELLING GOES INTO EFFECT IN MEXICO

The labeling will allow consumers to obtain quick and easy information to help them make informed decisions about their intake of food components, identifying products with seals indicating “Excess Calories,” “Excess Sodium,” “Excess Saturated Fat,” “Excess Trans Fat,” “and “Excess Sugar.” In addition, in the case of foods that so contain the additives, they are to be marked “Contains Caffeine – To Be Avoided by Children” or “Contains Sweeteners – Not Recommended for Children.”

The idea of the amendment, apart from providing consumers with clear and direct information, is to encourage the food industry to modify the makeup of their products and so to avoid the use of the stamps on them. The amendment also presents an implementation plan in three phases, intended to tighten labelling requirements by the year 2025, when the quantity of the abovementioned nutrients will have to be even lower to avoid the application of the stamps.

A model generated by Mexican researchers predicted that labeling could reduce consumption by up to 36.8 kcal per day, translating into a 4.98% decrease in the prevalence of obesity among adults under the age of sixty. This strategy is estimated to reduce 1.3 million cases of obesity and save $1.8 billion in costs associated with the condition.

Taken from NOM-051-SCFI/SSA1-2010 Sources: MODIFICATION to the Official Mexican Standard NOM-051-SCFI/ SSA1-2010, General Specifications for the Labeling of Prepackaged Foods and Non-Alcoholic Beverages Commercial and health information, published on April 5, 2010. Official Gazette of the Federation, 2020.

LATEST NEWS

On 27 March 2020, the Diario Oficial de la Federación, the official government gazette, published its modifications to NOM-051-SCFI/ SSA1-2010 of the General Specifications for Labeling of Prepackaged Foods and Non-Alcoholic Beverages, originally published on 5 April 2010. These include more “aggressive” front labeling in terms of mandatory nutritional information for all products marketed in Mexico, whether they are produced in Mexico or not.

In response to the high rates of obesity and chronic-degenerative diseases in Mexico, the federal government has implemented modifications in the way it communicates the nutritional content of packaged foods and beverages.

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A F R I C A E R A D I C AT E S P O L I O AFTER TWENTY-FOUR YEARS, WITH NO REPORTED CASES

LATEST NEWS

After the World Health Organization designed a plan in 1993 to eradicate polio through immunization in forty-one different countries in Africa, through massive oral vaccination campaigns twice a year, on 25 August 2020 the same organization issued a press release stating that Africa was certified free of wild polio.

In achieving the required nine billion oral vaccines, 220 million children were vaccinated in multiple doses, along with two million volunteer vaccinators who supported the campaign from 1996 to 2020. The initial projection planned to eradicate the disease by 1999, but the task took twenty years longer than expected.

Today, only two countries in the world still have wild poliovirus transmission, namely Pakistan and Afghanistan. Measures for immunization should not therefore be relaxed, as the virus could be imported from these countries again.

Sources: World Health Organization. Global polio eradication initiative applauds WHO African region for wild polio-free certification. News. 2020. www.africakicksoutwildpolio.com

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LATEST NEWS

Picture: Sunday Alamba

Written by Dr. Carmen de la Rocha D. in Plant Biotechnology, CINVESTAV-Irapuato - Master of Science in Biochemical Engineering, ITC - Bachelor of Science in Nutrition and Food Science, IBERO, Leรณn - Supervisor of the Department of Development CidVID - Professor of Subject B, CUCS UdeG Member of the National System of Researchers, level I.

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LATEST NEWS

Tat to o Ink for Canc e r D etectio n

A colorful approach to the development of new nano-based image contrast agents designed to improve cancer detection.

Early detection of cancer is essential to improving disease prognosis and quality of life for people with cancer. This article discusses the possibility of finding ink-based compounds to “color” tumor cells and differentiate them from healthy cells.

The development of new imaging methods could provide timely detection of cancer during routine screenings or help oncologists identify tumor margins for surgical resection.

Time is a key factor in the diagnosis of cancer. Early screening for malignant and precancerous lesions has been shown to reduce mortality greatly.

Helen R. Salinas and her collaborators at the University of Southern California and the

University of Texas Health Science Center evaluated the optical properties of a colorful class of ink and pigments that humans routinely use: the tattoo inks and pigments that the FDA has approved for coloring foods, drugs, and cosmetics. Their absorption, fluorescence, and Raman scattering properties were characterized in the hope of identifying a new panel of dyes offering exceptional image contrast. Some dyes, such as “optical inks,” were found to exhibit multiple useful optical properties, surpassing some of the clinically approved imaging dyes on the market.

Obtaining negative tumor margins (which corresponds to the complete removal of the tumor) can be essential to a patient’s survival.

Developing new imaging techniques with increased sensitivity to cancer allows for timely medical intervention and better results for patients. Molecular imaging is an imaging strategy that uses contrast agents, along with various imaging modalities.

In order to transport the dyes to the tumor, the researchers designed biocompatible and biodegradable liposomal nanoparticles.

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Liposomes are spherical vesicles with a double lipid layer, similar to cell membranes, capable of encapsulating the pigments. The pigments passed through the blood vessels and penetrated the tumor tissue, where they were retained in different models of lymphoma, colorectal cancer, and cervical cancer. The molecules of the dyes, administered in their free form (i.e. not encapsulated), also accumulated in the neoplasm. The researchers concluded that administering them during removal surgeries would help surgeons to identify the limits of the tumors and to eliminate them effectively. If so, this would be the first step in developing commercial dyes combined with nanovesicles designed to detect cancer in a timely manner.

Source.

Salinas, H. R., Miyasato, D. L., Eremina, O. E., Perez, R., Gonzalez, K. L., Czaja, A. T., Burkitt, S., Aron, A., Fernando, A., Ojeda, L. S., Larson, K. N., Mohamed, A. W., Campbell, J. L., Goins, B. A., & Zavaleta, C. (2020). A colorful approach towards developing new nano-based imaging contrast agents for improved cancer detection. Biomaterials Science. https://doi.org/10.1039/d0bm01099e https://www.investigacionyciencia.es/noticias/tinta-de-tatuaje-para-detectar-el-cncer-18981

LATEST NEWS

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DRUGS TO PROMOTE O R G A N S U R V I VA L I N E L D E R LY D O N O R S

LATEST NEWS

Senolytics prevent inflammation induced by mitochondrial DNA and promote the survival of aging organs after transplantation.

Organ transplantation is the treatment of choice for patients with irreversible endstage organ failure. Organ donation is limited, however, resulting in long waits during which many patients die or become too ill to be eligible for transplantation.

Currently, the foremost strategy with a potential for ending this long wait between supply and demand is to allow the use of organs from older donors, but these are now frequently discarded. Recently, it has been shown in clinical and preclinical studies that advanced donor age poses a risk of adverse outcomes. But what if there were a way to rejuvenate these organs?

Aging is associated with an increased load of senescent cells that are associated with chronic low-grade inflammation.

Transplants, even with a small amount of

senescent cells in young recipients, cause deterioration in function. Aging cells have been shown to contribute to a decline in cardiac function and resistance to stress. Recent studies, however, suggest that circulating mitochondria and mitochondrial DNA may mediate early allograft dysfunction.

A study by Iske Jasper and collaborators from the University of San Francisco showed that the activation of cluster differentiation in aging is caused by a systemic increase

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in levels of free mitochondrial DNA from cells communicated through TRL9, which promotes Th1/Th17 immunogenicity after ischemic reperfusion injury. Moreover, senescent cells have been identified as a key source of mitochondrial DNA. Finally, treatment with senolytics (Dasatinib plus Quercetin [D+Q]) was shown effectively to eliminate senescent cells by reducing the burden of free mitochondrial DNA levels and age-associated inflammation and so specifically prolonging the survival of cardiac allografts in old mice.

These findings emphasize the clinical potential of senolytics in enabling the use of older donor organs for transplantation.

The authors of the study have concluded that the findings in mice could also occur in humans; if so, senolytic drugs would provide new hope for facilitating transplantation in society.

Source: Iske, J., Seyda, M., Heinbokel, T., Maenosono, R., Minami, K., Nian, Y., Quante, M., Falk, C. S., Azuma, H., Martin, F., Passos, J. F., Niemann, C. U., Tchkonia, T., Kirkland, J. L., Elkhal, A., & Tullius, S. G. (2020). Senolytics prevent mtDNA-induced inflammation and promote the survival of aged organs following transplantation. Nature Communications. https://doi.org/10.1038/s41467-020-18039-x

ART & LITERATURE

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FEASIBILITY OF USING DEEP LEARNING TO DETECT CORONARY ARTERY DISEASE

LATEST NEWS

Coronary artery disease (CAD) remains the leading cause of death worldwide.

That is why accurate, practical, and cost-effective tools are needed to detect cardiovascular disease.

In addition to conventional predictive models, based on clinical risk factors, there are some facial features that are associated with an increased risk of cardiovascular disease, such as alopecia, gray hair, facial wrinkles, earlobe folding, xanthelasma, and corneal arch, so a predictive model could facilitate the timely detection of these diseases. The use of these facial features for disease detection has many limitations, however, owing to the few categories and low prevalence of facial features, lack of specific definitions, a quantifiable severity classification, and a low reproducibility in human identification.

This is why a group of Chinese researchers has created a learning algorithm that is a promising tool for timely diagnosis based on facial photos (selfies).

Shen Lin and collaborators from the National Clinical Research Center of Cardiovascular Diseases in the People’s Republic of China conducted a multi-center cross-sectional study

in which data from two studies performed in nine sites in China was obtained. Participants underwent elective coronary angiography or coronary surgery. Patients were photographed prior to the procedures, full face and in profile, using a digital camera with more than twenty million pixels. Interviews collected data on economic status, demographic situation, characteristics, lifestyle, family history, and medications used. The researchers concluded,

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who have undergone facial cosmetic surgery could show wrong results with the tool. They therefore consider it necessary to carry out more studies in order to develop and train algorithms with photographs for the global population. Nevertheless, this study is a novelty that offers hope for the timely diagnosis of one of the world’s deadliest diseases.

The study could be a first step in deciding whether to perform more accurate and expensive medical tests in order to confirm or rule out the diagnosis. The researchers also recognize, however, that the tool still has important limitations and needs further development to improve its specificity. With the present tool, many people who do not really suffer from coronary disease might be misdiagnosed, and this would unnecessarily overload health care systems.

Source: Shen Lin et al. (2020). Feasibility of using deep learning to detect coronary artery disease based on facial photo. European Heart Journal, 1–12. https://doi.org/10.1093/ eurheartj/ehaa640

The researchers mention that one limitation found in the study is that the algorithm suffers from a strong bias, since its learning has been focused on facial photographs of a single ethnic group: the Chinese. It is very likely that this tool would produce worse results in any other population group. Moreover, people

Written by Jennefer Iveth Mercado Cerda Student of the Master of Public Health, Bachelor of Public Health, Researcher in the Department of Development at CidVID.

LATEST NEWS

for the first time, the feasibility of algorithms for detecting cardiovascular and coronary heart disease through facial photos as a method for the general population and as a way of assessing the risks of this disease in healthcare facilities. This is a timely diagnostic tool vulnerable populations in developing countries to detect heart disease in time.

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AT T H E E N D O F T H E C H A I N THERE ARE PEOPLE Dante Alducin

THE EXPERT’S OPINION

Q.F.B. with the Specialization in Leading People and Teams program by the University of Michigan. He has 12 years of experience in Clinical Research. Founder of Blast!

Academy and host of the Ruido Blast! podcast.

One day in 2012 my cell phone rang, I was on one of those endless work tours around the country that I was doing over and over again as a clinical monitor. I wasn’t expecting any kind of important calls; I had dozens of them a day.

But even today, I remember what was one of the most disturbing tests I had to overcome in my entire career. The headquarters of the pharmacist for whom my company worked had decided to discontinue the only active patient in a very old breast cancer study. They needed the doctor in question to terminate his only patient, so they could close the study.

Usually there would be no problem, except

that this patient was still being treated and if the medication was withdrawn, the disease would probably return.

The doctor confirmed my suspicions, if they took her off the medication, the patient had a good chance of relapsing and eventually dying.

How did we get into this situation? One of the biggest questions I have had for so many years is how, in an environment dedicated to the health of patients on a daily basis, we forget that we are dealing with people. Not only from the health staff to the patients, but among ourselves as a team. I don’t think there’s a

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simple answer to that question, but a lot of it has to do with the unrealistic expectations that research teams are charged with. Such pressure, in one form or another, forces teams to take increasingly drastic measures in favor of metrics.

Over time, medical records have taught me many types of dramas, some with happy endings and some with less. But they focused me on what was the crux of my work: helping patients have a better quality of life and, in many cases, see another day. I believe that if all the great chain

Reversing that decision became my personal crusade, we teamed up with the doctor, we had calls with people from places and positions that I didn’t even know existed, we presented data, we negotiated: in the end they granted the patient compassionate use. Fortunately, I can say that in so much time as a monitor I rarely found myself in a situation of this level. However, it is this type of scenario that makes you see the undeniable importance of your work and the difference you can make. My wish is that every member of this research chain can see the difference it makes in their day-to-day work and the impact it can create to make this world a better place.

THE EXPERT’S OPINION

In 10 years as a monitor, I have done more than 12,000 trainings in the companies’ systems and there is not one that teaches you how to focus and sensitize yourself to see that, above all, we are dealing with human beings. You can go over the GCP ́s, the regulations and the ethical conditions a thousand times, but it is only seen as a compulsory and distant subject. It is repeated so much that it becomes meaningless.

of people who contribute to this could constantly see the result of their work, we would have better results, many fewer errors and we would enjoy our day-to-day life more.

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ON ETHICS AND CLINICAL RESEARCH Dr. Guillermo Caletti, Ph.D Chief of Clinical Operations at Boehringer Ingelheim for Mexico and Central America.

THE EXPERT’S OPINION

The development of technology and new medical treatments undoubtedly involves all members of the community, not only medical researchers, doctors and nurses, and other hospital staff, but also society in general.

The unquestioned need of human beings to overcome physical pain or mental suffering and to prolong life drives a continual search for treatments that can help us bear both the physical ailments themselves and the anguish and uncertainty that often accompany them.

Sometimes a sense of desperation, caused by ignorance and lack of knowledge of our illnesses, makes us rush our decisions and even to commit injustices and abuses against others.

How can we avoid seeking to benefit a loved one or ourselves over the interests and benefits of our fellow human beings? How can we render justice in society where medical treatment is coveted and expected by millions and yet available only to a few? How can we develop new therapeutic options without hurting those less fortunate than us along the way?

The development of new treatment options, especially drugs, designed to address doctors’ questions that remain unanswered, requires the investment of millions of dollars over very long periods of time (Figure 1).

Figure 1: Source:https://portal.unidoscontraelparkinson.com/medicamentos-parkinson/1639-parkinson-farmacosnuevos.html

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There are two primary objectives that must be demonstrated in the development of any new treatment: the efficacy of the treatment and its safety. This means that it will not only help to solve or mitigate some medical issue, but also not cause harm to the people who are going to receive it. In other words, it must be demonstrated that any risk of receiving a new drug is clearly offset by the benefit caused to those affected.

This kind of research demands a large investment of both money and human resources. It is normally financed by the international pharmaceutical industry and/or academic medical institutions which, through medical groups and specialized care clinics, work to develop the research protocols around the world.

The medical specialists who collaborate on these development projects invite patients suffering from the condition in question to receive the treatment under investigation and to allow themselves to be surveilled during the time established in the project. In this way, doctors collect information from patients all over the world, under strict quality standards, which then allows developers to draw valid conclusions about whether a medical treatment is effective or not and ―no less important― whether it is safe or not.

Before initiating a clinical research protocol, the country’s regulatory and health authorities must review documentation that describes the intentions of the research and that allows them to determine a) whether there is sufficient medical data to justify research on human subjects, and b) whether there are any other treatment alternatives with which the benefits and potential harms proposed by the research in question might be compared.

This is where the ethical principles of “beneficence and non-maleficence” strictly apply, making it possible to determine whether the treatment in question has the objective of benefiting the patient without causing harm or, as we have expressed it above, whether the benefits outweigh the risks.

Each country has its own system for reviewing and authorizing research protocols. In general, with small variations, this consists of a research committee, normally located in the health institution that will carry out the clinical trial, whose main objective is to validate the scientific purpose of the project, ensuring that its approach is consistent with the medical and scientific knowledge available at the present time.

THE EXPERT’S OPINION

But how do you prove the safety and effectiveness of a new medical treatment? The best way to do this is through clinical research studies, which require the participation of expert physicians and of patients suffering from a given unresolved medical condition.

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THE EXPERT’S OPINION

There is also a research ethics committee, or simply ethics committee, which ensures that the rights of the patients participating in the research are respected and that the project information given to each one of the participants is complete and understandable, allowing them to make an informed decision about whether or not to participate in the study, so that their human rights are in no way violated.

The process of reviewing and authorizing a clinical research project can take between two months and a year (or sometimes even longer), depending on the efficiency of the process and the variants considered in the review by the various agents, simultaneously or sequentially.

In order to harmonize the activities of global pharmaceutical development, in 1996 the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) was established to draw up guidelines for good practices in the manufacture, distribution, and development of pharmaceutical products for human use, with the collaboration of the European countries, the United States, and Japan. The E6 guide, revised in 2016, deals with, among other things, clinical research protocols and the participation of medical specialists (known as clinical investigators) and of their patients as participants in the research. It makes clear that participation in a research project is voluntary, that individuals may not be compelled to

participate in any way (or encouraged through payments or other benefits), and that they may stop participating at any time, without detriment to their health care.

No medical discovery or need for treatment justifies an assault on a person’s integrity or freedom of decision. A person should not be pressured to participate in a research project on the premise that it is the only available treatment option for his or her condition. What we in the medical and research professions must do, within an ethical, humanistic, and scientific framework, is to provide all available information about the new treatment, both risks and benefits, and let the person decide whether to participate in the research or not.

This decision should be free and voluntary.

The physician treating a patient, when inviting him or her to participate in a clinical research project, should think of the benefit to the patient and consider that the center of the decision, rather than the scientific knowledge in itself. The premise primum non nocere, which means “first to do no harm,” attributed to Hippocrates, should always be considered in scientific research. This will ensure that any medical research procedure has as its main purpose the benefit of those affected by it, with the certitude that we will not harm their physical, mental, or social integrity more than the disease itself has already done.

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T H E S C O P E A N D R E L E VA N C E OF CLINICAL RESEARCH Federico Lerner

ART & LITERATURE

Operations Director at LatinaBA, a regional CRO; and President of CAIC, Argentine Congress of Clinical Research. Dr. Lerner was responsible for leading many different clinical research teams for the first time to conduct large global registry trials, he was a former Latin American chief of four major global CROs.

For all of us who work in science, it is a basic tenet that scientific and technological advances generate progress in our society. We have learned in our day-to-day lives that bringing this sense of science to the general population is our duty. We have clearly realized, over the last few decades, more through errors than by lack of development, that this explanation and popularization of science, which support clinical research, is an obligation.

People do not generally read scientific publications for pleasure. Today only those who are working on a given subject have the capacity to understand concretely what is being expressed in scientific articles. They are not easy reading, often filled with scientific nomenclature or even complex formulas, incomprehensible to those who are not in the field.

One of the best definitions of science I know defines it as the generation of knowledge, but the knowledge obtained does not necessarily provide a benefit to society. Especially in health issues, there are numerous examples of studies that replicate previous findings, repeat things already known, or lack methodological support.

Their results are simply not valid.

I believe that in this way clinical research can be methodically formulated in order to generate knowledge that can be applied as a benefit to our society. Clearly, it will not happen overnight, but it is a basic principle that the subjects

participating in the research have a potential benefit and that society can benefit from that knowledge generated.

Throughout our history, and especially over the last two hundred years (to set a rather arbitrary date), society has seen the greatest scientific findings in the field of health care.

Van Leevwenhoeck and Spallanzani began the era of microbiology, putting a number of “living beings� in the dock as responsible for numerous diseases. Koch, with his postulates, classified matter as living or non-living (within the scope of his time). In the late 1800s and early 1900s, Paul

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Ehrlich formulated perhaps the best definition of the target molecules in pharmacological therapeutics, identifying “the magic bullet” as the one that would exclusively destroy microbes and thus developing, after having evaluated hundreds of active principles, the first arsenicbased compound to treat syphilis, the now famous compound 606, the p,p’-Dihydroxydiaminoarsenobenzene.

In other words, clinical research in particular generates risks. I am not referring specifically to therapeutic failures for a particular subject, since this can also occur in normal medical practice, but rather, for example, studies that generate negative results, those that fail to detect adverse effects with a very low incidence, and methodological or recording errors.

LIFE EXPECTANCY

CLINICAL RESEARCH & PHARMACOLOGY

Without detailing a long list of biomedical advances in recent years, it might be noted that, thanks to clean drinking water and proper sewage and waste treatment, along with the development of drugs and vaccines, life expectancy has increased nowadays to between sixty and seventy-five years in Latin America. (In global terms, there is an enormous disparity in this value, depending on the country under consideration, and ranging from thirty years in sub-Saharan Africa to over ninety years in the Principality of Monaco). What is certain,

however, is that life expectancy at the end of the 1800s was no more than thirty-five years and had been stable since the Middle Ages.

Although scientific health research has improved both life expectancy and quality of life, not everything has been necessarily positive. Research means evaluating something of which we do not know the result, and although this may seem obvious, the results can be good (ratifying the hypothesis raised) or bad (rejecting it). In fact, if we knew what the outcome of pharmacological research would be, it would simply be unethical to carry it out.

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CLINICAL RESEARCH & PHARMACOLOGY

Basically, there are many more potential therapeutic molecules that do not continue to be developed than those that reach the commercial market. This is due either to lack of clinical efficacy (and the consequent risk of treating a patient population with a treatment that is not effective, or less effective than its comparator) or to safety problems (the participating subjects received a treatment that caused them an adverse effect).

In both cases, these are the risks associated with performing science.

Over the last few decades there have been some examples of safety problems, one of the best known being the increased cardiovascular risk (myocardial infarction and cardiovascular

accident) due to the use of celecoxib (in view of the imbalance of endothelium-platelet functions).

Scientific research should be carried out in accord with a strict risk/benefit assessment for each protocol and the precept of doing no harm should always prevail. But I would like to close this small article by mentioning just two of the countless positive results of clinical research.

According to the World Health Organization, it is estimated that vaccines currently save the lives of some three million people a year and that tens of millions were saved by the discovery of antimalarial drugs. It is up to all of us to continue this legacy and to generate more scientific knowledge, in order to improve the quality of life for generations to come.

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WHERE DRUGS AND MEDICINES COME FROM A BRIEF ACCOUNT OF THE DEVELOPMENT OF PHARMACEUTIC AL S Arieh Roldán Mercado Sesma

Summary According to data from the pharmaceutical industry, of every 10,000 molecules evaluated for transformation into some kind of medicine, only one to three of them will make the grade. The development of pharmaceuticals is a continuous and changing process, with different byways and nuances whereby the search for a molecule or substance with pharmacological potential, whatever its origin, goes through various phases of testing for safety and effectiveness, leading finally to a drug for human consumption.

Introduction A probability of one in ten thousand would be acceptable to almost no one.

In simple human terms (and not mathematical ones) it would mean possibly waiting almost twenty-seven years to find a solution to a problem, if you tried out a new solution every day.

You might have to read 9,999 books before finding your favorite author or the precise quotation that describes your emotions. The same number of television series might be necessary for you to say you like one of them. And yet this is the kind of probability that a drug or medicine has of eventually being marketed.

According to data from the pharmaceutical industry, of every 10,000 molecules evaluated for transformation into some kind of medicine, only one to three of them will

make the grade. During the process, some of them will lose viability in the first stage, and others perhaps when they are nearly ready for sale to the public. Still others will achieve their goal of being marketed, but in real-life circumstances they will end up being withdrawn for reasons of safety or owing to various commercial considerations.1

CLINICAL RESEARCH & PHARMACOLOGY

is a surgeon and obstetrician graduated from the Universidad de Guadalajara. He studied at the Centro Universitario from 2000 to 2006, earning a master’s degree and doctorate in pharmacology. He has been an associate professor and researcher at the Centro Universitario de Tonalá (Universidad de Guadalajara) since 2012 and is a member of the Sistema Nacional de Investigadores (Level 1).

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Our children may ask us (or we ourselves may have asked, as children): “What tree do medicines grow on, or where are they found?

Are they all created in laboratories?” As adults, our questions may circle about the seemingly inexhaustible capacity of the pharmaceutical industry to create new medications. What strategies are employed by “laboratory scientists” to ensure that there is always some new pharmaceutical in line, waiting to be transformed into a medicine?

CLINICAL RESEARCH & PHARMACOLOGY

Definition and Organization The development of pharmaceuticals is a continuous and changing process, with different byways and nuances (by no means as rigid as one might imagine), in which the search for a molecule or substance with pharmacological potential (preventive, palliative, curative, diagnostic), whatever its origin (vegetal, animal, mineral, synthetic), goes through various phases of testing for safety and effectiveness, leading finally to a drug for human consumption.2 The stages or phases may differ in number, depending on the regulatory agency in question, but they generally include at least three stages: 1.Chemical development or characterization stage 2.Preclinical stage 3.Clinical stage: Experimentation on human beings

Chemical Development or Characterization Stage The chemical development stage involves the discovery, characterization, and final formulation of molecules with pharmacological potential. In practical terms, during this stage, researchers explore and examine “nature” (with a touch of serendipity, on occasion) with a view to discovering and extracting chemical candidates which, by their effect either on their organism of origin or on their external environment, modify a biological variable or entity.

To take an example, in order to make this more clear: a researcher working in a laboratory may attempt to find a substance (let us assume the term “antibiotic” does not yet exist) that inhibits or eliminates the growth of bacteria that generate deadly diseases in human beings. By chance or serendipity (or a combination, perhaps, of serendipity and curiosity), the researcher has to leave the laboratory for a few days and forgets his (or her) Petri dish on the worktable. On returning, before throwing away the contents of the dish, he notices something strange. He takes his microscope and observes that the bacteria have not proliferated, owing to a fungus introduced from outside of the dish.

With the help of other member of the laboratory, he identifies the culprit: a fungus of the Penicillium family.

The rest is history.

The goal of this stage is to generate stable active principles with a potential for being transformed into a medicine.

Preclinical Stage During this stage, the toxic effects of the molecule obtained in the characterization stage is evaluated at different levels. These trials tend to be performed in organoid and/ or animal cell cultures. It is currently possible to run predictive mathematical models on a computer in order to examine the possible outcomes of the interaction of the active principle with a living organism or with a system or organ thereof. The exploration of this contact may result in the union of the pharmaceutical with a certain protein, yielding data on the strength and time of union, among other factors. Nevertheless, these results do not yield sufficient evidence to be used as a sole source of information.

Organoids are relatively new, consisting of threedimensional cultures that imitate the structure and function of an organ. Put more simply, they are organs in miniature. Experimentation of this type can be performed during the preclinical stage or later. The objective is to reproduce the effect of a pharmaceutical on an “organ” without the intervention of other physiological variables that may exist in the case of an organism as a whole.

The evaluation of this effect can be very useful.

In spite of the foregoing, the most traditional way of carrying out this stage is through animal models. These can be either small (inferior) species or large (superior) species, depending on the size and complexity of the living being. The choice of model, that is, of species to be used generally depends on the active principle, its effect (mechanism of action), and its similarity to a human being.

Such models can be evaluated wholly or partially (limited to a single organ).

CLINICAL RESEARCH & PHARMACOLOGY

Following the discovery of the substances with biological effects, it is necessary to continue with their characterization, that is, to identify and reconstruct the active principle of the substance, the molecule capable of modifying a physiological variable. Once this has been achieved, it is important that the molecule in question be stable in actual conditions, and above all that it be easy to extract or synthesize, without any loss of its pharmacological characteristics. In general terms, a pharmaceutical can be of vegetal, animal, mineral, or synthetic origin. It may be an extract from some part of a plant (as for example arrow poison curare, extracted from Chondodendron tomestosum), or the secretion from an animal (protamine, for example, extracted from the sperm of certain fishes), or a substance derived from a metal (such as iron fumarate), or simply generated in the laboratory from an animal extraction (as in the case of insulin). In short, the range of “possible” pharmaceuticals is enormous.

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CLINICAL RESEARCH & PHARMACOLOGY

ART & LITERATURE

For example, let us suppose a researcher wishes to understand the effect of seawater as a possible ocular lubricant. He may choose a white rabbit as an animal model, since the eyes of this species are very similar to human eyes. But if the researcher wished to evaluate the effect of the same active principle on the heart (since certain rabbits show an accelerated heartrate), the best animal model might be a pig. Be that as it may, many experiments are performed on different strains of rats and mice, simply because they are so easy to handle.

It is also possible to use animal models to carry out trials of the active principle that has been extracted on the conditions for which it is intended. There are two options here: generating the model itself, or acquiring it. In the first case, it is possible to “create” a sick rat in order to imitate humanlike physiopathological phenomena. In the second case, it is possible to acquire a genetically manipulated animal model (known as a knockout) that shows a physiological defect. Another example to illustrate this: let us suppose a researcher wishes to undertake trials of a new kind of insulin. A laboratory mouse is created and injected with streptozotocin, a substance that destroys the beta cells of the animal’s pancreas, which produce insulin. In the other case, the researcher will purchase a knockout mouse for the insulin gene.

The goal of this stage is to evaluate general and specific toxicity (that is, whether the pharmaceutical affects the entire organism or only certain tissues), relative efficacy (the mechanism of action and its effect are corroborated), and certain pharmacokinetic parameters (how and where the substance is absorbed, stored, transformed, and eliminated).

Clinical Stage: Experimentation on Human Beings This stage tends to be the most crucial of all in the development of pharmaceuticals, since, if the potential harm exceeds the benefits, however slightly, it is very probable that the regulatory authorities will reject continuation of the trials through the following phases, owing to the fact that, as the involvement of human subjects grows, both costs and required supervision tend to increase. This stage is usually subdivided into four phases, although there are sometimes further subdivisions. These are the phases commonly referred to as clinical trials.

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Phase 1 or Pharmacokinetics (PK) During this phase, which tends to involve few participants (~5-30) and last from anywhere from a few days to several months, the subjects are usually in good health. The volunteers who participate in this phase are often hospitalized or interned in some way so that the great majority of variables can be evaluated and the number of intervening or confounding variables that might modify expected results can be diminished. Among all these variables, the goals to be controlled include: feeding,

laboratory proofs, physical activity, exposure to environmental and emotional factors, and others. The most controlled factor, however, is strict adherence, whereby the participant ingests the trial drug or has it applied in some other way (intravenous, intramuscular, etc.).

No placebo or any comparable substance is necessary to contrast results.

Phase 2 or Safety Over Efficacy In this phase, which normally lasts several months, the number of participants tends to increase to anywhere from ten to a hundred, approximately. Trial participants are usually sick, diagnosed either with the illness for which the pharmaceutical is being evaluated or with some similar condition. The experimental treatment or intervention may be administered in the context of ambulatory care or hospitalization. Since strict safety is the goal, laboratory and consulting room testing is frequently done. It is recommended that a second group be given a placebo or a medicine of proven efficacy, already in use, for the purposes of comparison.

CLINICAL RESEARCH & PHARMACOLOGY

The objective of this phase is to determine safety and pharmacokinetics. The endeavor to identify all the possible adverse effects the pharmaceutical may have on a human being requires a large number of laboratory and consulting room tests. It also includes coming to understand how and where the substance is absorbed, stored, transformed, and eliminated.

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The goal of this phase is to evaluate safety and certain aspects of efficacy. As in the prior phase, the main adverse effects are monitored through repeated laboratory and consulting room testing.

CLINICAL RESEARCH & PHARMACOLOGY

Phase 3 or Efficacy Over Safety This is considered one of the most important phases, since the pharmaceutical being tested must show its superiority (or at least a modification of the response variable) with respect to whatever it is being compared to. In this phase, participants can increase to anywhere from hundreds to thousands, though this will depend on the prevalence of the illness and the budget available. This phase tends to last several years. In order to sustain and corroborate results, numerous clinical trials, with different outcomes and comparisons, tend to be held. As in the previous phase, participants have been diagnosed with the condition the pharmaceutical is designed to “treat.” It is recommended that a control group, whose members have been administered a placebo or a drug of proven efficacy, also be employed.

Unlike the previous phase, the goal here focuses mainly on effectiveness and, to a lesser degree, safety.

Phase 4 or Past-Marketing During this phase, clinical trials are no longer performed. Rather than experimentation with human subjects, an evaluation is performed of all the data accumulated on the actual use of the medication, including reports of adverse effects or reactions that have appeared during the period of its marketing and reallife circulation. There is no recommended or approximate number of participants, but

since the drug is already being marketed, they can be expected to number in the thousands.

The duration of this phase tends to be by periods of anywhere from two to five years, or even up to ten years. It includes participants suffering from the condition for which the drug is specifically prescribed, but also offlabel prescriptions. Comparison groups are not normally employed.

The main goal is safety, though new hypotheses may be generated from the use and effects of the substance in real life conditions.

Final Comments Few of us ever ask ourselves where the drugs and medicines come from that we use in our everyday lives. But with the advent of the SARS-CoV-2 pandemic, we have all been given a crash course in pharmaceutical research in real time. We have gone from discovering a few cases of an untypical illness to the development of a vaccine, moving from the identification of risk factors to clinical trials with human subjects. More than ever before, we have paid attention to the development of pharmaceuticals. This process that we are experiencing in accelerated motion ―from discovery to clinical trials― usually lasts about ten years. It tends to cost billions of dollars and have a relatively low success rate.

In the case of success, however, those costs can be quickly and significantly recovered. As in Maurice Sendak’s book, Where the Wild Things Are, the time span for the development of drugs and medicines may seem long, but it is very short if considerations of safety are taken into account.

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Conclusion Thanks to these development, safer and safer drugs have been created and tragedies like that of the thalidomide babies have been avoided.

There is still much to improve, however, in areas such as animal experimentation, human exposure to risk, and long-term safety. We need to speed up certain stages of the process, but without compromising strict attention to safety.

Further Reading 1 By “real life” we mean simply everyday life, excluding the controlled environment, in terms of almost all variables, generated not only in research on plants and animals, but also in experimentation with human subjects.

2 For the purposes of this article, we use the term pharmaceutical for a substance which does not yet have a definitive form and has not been marketed. A substance with a final pharmaceutical form, which can be marketed, is referred to as a drug or medicine. But either kind of substance may have potential uses in the context of the health sciences.

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Clevers, H. “Modeling development and diseases with organoids.” Cell 2016;165:1586-1597.

Lancaster, M. A. and J. A. Knoblich. “Organogenesis in a dish: modeling development and disease using organoid technologies.” Science 2014;345(6194):1247125.

Robinson, N. B., K. Krieger, F. Khan et al. “The current state of animal models in research: a review.” Int J Surg 2019;72:9-13.

Walsh, C. T. and R. D. Schwartz-Bloom. Levine’s Pharmacology.

Drug actions and reactions. 7th edition (Taylor & Francis, 2005).

Welch, A., R., R. Salomon, and S. Borouman.

“Biopharmaceutical drug development pillars: begin with the end in mind.” Clin Pharmacol Ther 2019;105(1):33-35. <https://www.ema.europa.eu/en> <https://www.fda.gov/drugs/development-approval-processdrugs> <https://www.gob.mx/cofepris/acciones-y-programas/ registros-sanitarios-de-medicamentos-84937>

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Medical Ethics at the Present Time

INTERVIEW

Interview with Dr. Ana Luis Caballero Elvira, chairwoman of the ethics committee of iBiomed My name is Ana Luisa Caballero Elvira. I am Mexican and hold an undergraduate degree in clinical nutrition from the Universidad del Valle de Atemajac. Shortly after graduating, I was invited to collaborate as a clinical trial coordinator. At first I imagined this would involve work as a researcher, developing protocols and putting them into practice. In fact, a very different type of work awaited me, both astonishing and highly satisfying, as the development of new pharmaceuticals involves a great deal of background work that few of us are aware of.

Moreover, there is the satisfaction of helping patients and even becoming a part of their lives.

After working for three years as a dietitian/nutritionist in the nutrition department of the Instituto Mexicano del Seguro Social, the Mexican public health system, I had the opportunity to become assistant head of the department and also to teach internal courses on various subjects. I was recently selected to coordinate the undergraduate program in applied nutrition, which the institution offers as part of its strategic ongoing training plan for its employees.

Nevertheless, for personal reasons I decided to continue to work as a clinical trial coordinator, accepting an invitation to join the iBiomed team. I am grateful to the director for his confidence in me and for a subsequent invitation to join the ethics committee, where I began by acting as secretary. I am currently chairwoman of the committee.

Mexico definitely remains a developing country, especially in the area of health care. One proof of this is that the expected life span of Mexicans has gone from 42 years in 1940 to 75 years in the year 2000 (1).

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To what do you attribute this development in Mexico?

Looking at the other side of the panorama, what do consider the areas of opportunity for improving the Mexican public health system?

The foremost area of opportunity for improvement is increasing the number of doctors in accordance with population growth, as well as the creation of better health programs, so that all Mexicans can have access to new treatments, whether these involve actual cures for their ailments or simply improved quality of life.

In general terms, could you offer a personal definition of the notion of medical ethics?

From my own experience, I can say that it is the care of the patient within a framework of values acquired in the whole course of our lives, starting primarily from the education we receive at home.

It involves not prioritizing the progress of science by putting vulnerable populations at risk. We have to forget about achieving the recognition of the medical community, and we have to remember the oath we took in order to become part of that community: the promise to use our knowledge and skills to safeguard the health of patients.

To what extent do you believe that future progress in science and medical technology will be compatible with the dignity and centrality of the human person?

INTERVIEW

I attribute it mainly to development in the area of medicine in general, thanks to which all Mexicans have had access to social security and medical attention in public hospitals, as well as to various specific programs that have been developed in the course of our history. These include programs established by presidential decree and of course the development of new treatments, particularly for chronic-degenerative diseases. This development also has very largely to do with the improvement of basic services in the home, such as clean drinking water, which is of vital importance in preventing gastrointestinal illnesses, which used to be lethal.

I believe there is still a long way to go before the paths will converge. Technology has ceased to be a support for human beings: in the contemporary world, it has become the focus of everything. We have to pay more attention to our surroundings: to the consequences, for example, of generalized access to the internet. It is true that this has opened up frontiers all around the world, facilitating global communication and remote work, but at the same time social media can prevent us from communicating directly with one another. We may be in a meeting, but with our eyes glued to our smartphones, rendering our everyday lives a virtual reality in every sense. Technological progress and the implementation of mechatronics in the area of medicine have made certain surgeries faster and less invasive, but I come back to the same issue: that patient-doctor relations have also changed. I donâ&#x20AC;&#x2122;t wish to generalize, but doctors are sometimes more focused on the programs through which medical history can be made, and end up forgetting really to observe their patients, to focus on asking them questions and giving them the treatment that can alleviate their conditions.

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In short, we have also been dehumanized through all of this progress. We have affected our planet in the process, as well as ourselves, in our quest to live within a nonexistent reality.

INTERVIEW

We know that many developments in medicine and technology generate complex challenges: everything from the validation of cloning to the therapeutic use of cannabis to stem cell tissue engineering… As far as Latin America is concerned, what is the context (economic, sociological, political, and psychological) in which these issues can be best resolved in the future?

There is a serious debate about the participation of the all the spheres of reflection involved. Changes need to be made, or at least legislative measures need to be taken so that cloning and stem cell tissue engineering can be carried out upon the ethical foundations of our society. There are countries that already permit the use of these development for therapeutic purposes, such as the United Kingdom, Sweden, and France. As a result, I believe scientists interested in these matters will emigrate to those countries in order to be able to make use of their skills, or, for example, to the United States, where the use of public funds for such research is forbidden on moral and ethical grounds, but private investment is permitted. In this way, as I understand it, both approaches can be analyzed.

Therapeutic cloning through stem cells, on the other hand, has opened a path to regenerative

medicine, giving hope to people suffering from very serious conditions. The issue has provoked religious and ethical debates which cannot be resolved by most members of our society: we are facing a situation in which society has preconceived ideas and the superficial media treatment of the issue (typical of our era) does not help in achieving a consensus for allowing the progress and control of scientific knowledge on behalf of humanity. Neither must we forget the conflict over rights, the question of who shall have priority and who must assume responsibility for these choices. We need to reconcile respect for human dignity with the rights of patients to gain access to treatment, since both of these objectives contribute equally to the society in which we live.

In conclusion, I believe that the challenges facing us are too large and complex to be resolved immediately. They must be seen and analyzed as individualized problems. It is easier to find solutions for all through the application of pragmatism and common sense to circumstances as they arise.

(Interview conducted by the editor-in-chief of Clinical Research Insider.)

1 See José R. Narro, José D. Rodríguez, Carlos T. Viesca, and Luis Felipe H. Abreu, “Ética y salud. Retos y reflexiones,” Gaceta médica de México (Mexico City, 2004).

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Mexican Researchers Discover that Black Pepper May Have AntiViral Effects Against Covid-19 An interview with Dr. Juan Vázquez Martínez, head of a group of Mexican researchers who have discovered the anti-viral effects of black pepper in combatting Covid-19.1

Dr. Juan Vázquez Martínez, thanks to you and your team of Mexican scientists involved in the discovery, the somber outlook on the pandemic caused by the coronavirus begins to show glimmers of light. Could you explain the findings of your research to us?

We found that a group of compounds known as piperamides and alkamides have great potential for interfering with some of the key enzymes involved in the virus’s infection process: both the human enzyme ACE2 and the viral enzymes Mpro and RdRp. These compounds are found in plants, particularly those of the Piperaceae and Heliantheae families, representative members of which are black pepper and chilcuague (known as Azteca gold root), respectively. The best results were found among the dimeric piperamides, where

What exactly are the properties of the piperamides and alkamides, and what are their potential effects against the SARSCoV-2 virus?

In chemical terms, these compounds belong to the group of amides, or more generally to that of natural nitrogenous metabolites, which are bioactive in many systems and organisms.

In previous research, we have described the bioactivity of both alkamides and piperamides in bacteria, fungi, plants, and insects. There is also some evidence of their activity in viruses.

We therefore undertook to explore their potential effects against SARS-CoV-2.

What is the pharmacological potential of these inhibitors?

These compounds, especially pipercyclobutanamide B, have the potential to bind in a stable manner with the main protease of the virus (Mpro) and therefore to interfere with its activity. Mpro is one of the main non-structural proteins that enable the virus to complete its cycle within the cells. The function of Mpro is to cut the polyproteins, thereby producing the proteins necessary to the replication of the virus.

Moreover, an abs or ption, distribution, metabolism, and excretion

INTERVIEW

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has positioned itself as the disease of the twenty-first century.

By 13 October 2020, there were almost 38 million cases of infection around the world and more than a million deaths caused by it.2

pipercyclobutanamide B forms a complex with the viral Mpro. In the simulations we ran, this pipercyclobutanamide B-Mpro complex proved highly stable, making it the main candidate to be used as an antiviral against the virus.

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(ADME) profile and Lipinskiâ&#x20AC;&#x2122;s rule of five showed that these compounds have a potential as drugs for oral absorption by humans.

Mpro vs piperciclobutanamide B cardboard representation

INTERVIEW

What were the processes and techniques used to undertake the studies?

This part of the project consisted of computer simulations to determine the inhibitory potential of around 100 alkamide- and piperamide-type compounds against three enzymes related to the infectious process of the virus. The testing by our silicon friends included techniques of molecular docking, molecular dynamics, ADME profiling, Lipinskiâ&#x20AC;&#x2122;s rule of five, and Jorgensenâ&#x20AC;&#x2122;s rule of three.

Taken together, these molecular modeling techniques allowed us to make the predictions described for these compounds: the potential for inhibiting the replication of the virus and for being administered orally in humans.

What information or event motivated the research?

Can you suggest any follow-ups for ongoing research or future experiments?

The project was a response to the economic and social impact of the Covid-19 pandemic on different population groups. Following an exhaustive analysis of the information available at the beginning of 2020 about the antivirals proposed and approved to combat the virus, we reached the conclusion that many of these antivirals belong to the group of nitrogenous metabolites. They contain amide groups, cyclical and aromatic. Based on these observations, and our prior knowledge of the characteristics and properties of alkamides and piperamides, we considered the possibility of their use against the virus. We then put together a team of experts in toxicology, biochemistry, chemistry, chemical analysis, organic synthesis, natural products, and molecular modeling, whose joint contributions led to the results we have presented.

In our particular case, the path to follow is to continue with the synthesis or purification of the compounds identified in order to perform in vitro trials on inhibitory effects against the Mpro protease of SARS-CoV-2. We are seeking financing for this phase. In more general terms, ongoing research should focus on safe, efficient, and accessible vaccines, treatments, and medical protocols. Not only for this new virus, but also in order to prevent the appearance of more aggressive strains.

Is it possible to know what concentration or quantity of black pepper is required for its components to have the desired effect?

Yes, but there is still a lot to do. First of all it is necessary to determine the inhibitory effect of the pure extracts and/or compounds of

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the Mpro protease in vitro. Then to develop research protocols for trials on laboratory animals and/or humans. Once we know this, given that black pepper contains 1.2 mg per kilo of the more active compounds and around 50 mg per kilo of the less active ones, the calculation can be done. But we can already predict that it might be too much, so the ideal thing would be to purify or synthesize the compounds.

Judging from your own experience, what is the greatest challenge at present for scientists and researchers in their combat against Covid-19?

(Interview conducted by Clinical Insider Research staff writers.)

Juan Vázquez Martínez, the head of the research described in this interview, is a regular member of the American Chemical Society, holds Professional Development status in Mexico( PRODEP profile), and belongs to the Sistema Nacional de Investigadores of the CONACyT (level 1) and to the faculty of the Instituto Tecnológico Superior de Irapuato (ITESI-CA-8). He is also a researcher of the biochemical engineering education program of the Tecnológico Nacional de México (TecNM), ITESI campus. Dr. Martínez holds an undergraduate degree in biochemical engineering, with a focus on environmental engineering, from the Instituto Tecnológico de Morelia and a master’s degree and doctorate in plant biotechnology from the Centro de Investigación y de Estudios Avanzados of the Instituto Politécnico Nacional (CINVESTAV-IPN). He has also done postdoctoral work at the Natural Products Chemistry Laboratory of the CINVESTAV-IPN Irapuato and has been on the faculty of the TecNM/ITESI for two years, during which time he has worked on research projects dealing with the bioactivity of compounds of natural and synthetic origin, particularly esters and amides of unsaturated fatty acids. Others who took part in the research are Juan Manuel Gutiérrez Villagomez, Tonatiu Campos García, Jorge Molina Torres, and Mercedes G. López, in collaboration with the Institut National de la Recherche Scientifique (Canada) and CINVESTAV-IPN Irapuato.

2 “El mapa mundial del coronavirus: más de 37,9 millones de casos y más de un millón de muertos en todo el mundo” (13 October 2020), available online at RTVE.es: <https://www.rtve.es/noticias/20201013/ mapa-mundial-del-coronavirus/1998143.shtml> 1

Mpro vs piperciclobutanamide B surface representation

INTERVIEW

I believe the greatest challenge is to achieve a socially engaged science, which is to say: for science to be fully disseminated in and understood by society. For society in general to realize that we are all on the same team!

Most of us who dedicate ourselves to research are trying to contribute to the economic and technological development of the country.

We require greater investment in education, science, and technology, shared among all the educational institutions that perform research. We also need scientists to develop the capacity to transmit information so that it can be readily understood, moving away for a moment from technical language and using more colloquial language. This has to be done in a harmonious way, balancing the demands of researchers and needs of the public, with the government as the invisible interlocutor, whose main function is to encourage both first-rate research and the public dissemination of scientific knowledge.

In order to foster research sustainably in Mexico, we need accumulated investment programs with the guarantee that every centavo invested will positively impact some sector of society or some high-priority issue

in the short, medium, and long terms.

Owing to the importance of their research, the American Chemical Society made the original article by Dr. Juan Vázquez Martínez and his group of Mexican researchers, published in The Journal of Physical Chemistry Letters, available online (posted 25 August 2020): <https://pubs.acs.org/doi/10.1021/acs. jpclett.0c01685>

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THE HEROES OF CLINICAL RESEARCH

Dr. Arturo Ávalos

RESEARCH

Dr. Arturo Ávalos holds a master’s degree in bioethics and is the General Director of Ekomite.

In considering C. S. Lewis’s emblematic novel The Lion, the Witch and the Wardrobe (the first of The Chronicles of Narnia), it is worth comparing, from an ethical perspective, certain important aspects of the author’s narrative, which coincide, as it happens, with aspects of clinical research. And the fact that the novel belongs to so-called children’s literature should not devalue the conclusions drawn from this comparison.

The protagonists of the story, in the context of a war, are sent far from their homes and placed under the care of an old professor, who lives in a many-roomed mansion on the outskirts of London. In one of the rooms they discover a wardrobe that turns out to be the entrance to a parallel world called Narnia. Full of apprehension, Lucy, Susan, Edmund, and Peter undertake to explore this astonishing realm where the rest of the story unfolds.

Inhabited by a group of fantastical characters and governed by a “Deep Magic from the Dawn of Time,” Narnia has been awaiting the arrival of these “two Sons of Adam and two Daughters of Eve” as the fulfillment of a prophecy, as the White Witch seeks to subject the entire realm to her will. The arrival of

the children leads to a battle in which the inhabitants of Narnia, led by a lion named Aslan, confront the White Witch and her army of followers.

There is no need for more details for the reader to perceive the analogy. Clinical research is like the whole world of Narnia; each of its inhabitants like the different actors that make possible the development of new pharmaceuticals; the research subjects like the four young protagonists; the ethical principles and foundations that gave origin to the development of science are represented

by Aslan the lion; and all malpractice in general by the witch.

Thus, apart from relating each one of the characters as satyrs, centaurs, eagles, beavers, or dwarves (even when these show some similarities with certain researchers), it is worth reflecting, free of any influence, on the following: According to what principles do we exercise our activities as professionals in the field of clinical research? Because the mere fact of entering Narnia does not signify good fortune, just as neither does participating in a clinical trial bring benefits to all the subjects.

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vulnerability, especially in the case of those seeking a treatment. Of course, wielding power over others in order to cure them involves a greater responsibility, but to what degree are we aware of this solidary responsibility.

On the other hand, we can commit the mistake of justifying poor practices or of supporting unethical interests only if we focus on the magic and enchantments of Narnia, that is, on scientific and technological progress, even as we forget about the efforts, difficulties, and risks that the protagonists face. In other words, the development of new drugs has brought great benefits to many patients, but not to all. In the course of a clinical trial, if one of the protagonists fails or dies in the attempt, can we still say the story has a happy ending?

The answer is probably yes, but not for those who received a placebo, not for those who suffered some adverse side-effect, and not for those who may have been the victims of malpractice. In other words, although the sacrifice of a few for the benefit of a great many may be worthwhile, it is here that the bravery and heroism of those who participate as volunteers in a clinical trial come in play.

No less important than the lion and the witch, and an interesting element for the purposes of comparison, is the wardrobe.

As the gateway to Narnia, it resembles the vehicle whereby the first contact between a patient and a clinical trial is established.

Nowadays, patients may carry around their wardrobes with them, in the form of a smartphone, an iPad, or a laptop computer, and be familiar with the clinical trial even before participating in it. Although patients have access to more information than they used to, digital transformations and new tools of communication allow them to be contacted and even recruited for research projects.

But regardless of the means or channel of information, what is really important is not attempting to influence anyoneâ&#x20AC;&#x2122;s decision to participate or not.

The professional performance of a clinical trial involves complying with the various legislative standards and good practices apparently dictated by good sense, but in terms of ethics, there are still issues that require deeper reflection and cannot be addressed from a purely positivist angle. For example, to return to The Chronicles of Narnia, the need to conceal oneself in order not to be discovered (as a solution to a problem) is what led the four children to hide in the wardrobe. In the same way, when a patient is invited to participate in a clinical trial, his or her condition as a patient is the prime factor in making a decision.

Strictly speaking, all patients find themselves, to a greater or lesser extent, in a condition of

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In C. S. Lewisâ&#x20AC;&#x2122;s story, while his brother and sisters enjoy the friendliness and fraternity of the inhabitants of Narnia, Edmund, one of the protagonists, is seduced by the White Witch and used by her for her own purposes.

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Narnia awaited the arrived of our four heroes, but none of them was forced to enter: all of them did so of his or her own will, without knowing exactly what to expect (exactly as many patients become involved in clinical research). Now no less dangerous than direct coercion of a patient in order to obtain his or her consent is unconscious manipulation exercised by members of the clinical research world, who out of professional narcissism sees themselves as heroes to those who actually decide to participate in a clinical trial. Let us never forget that, both in Narnia and in the world of clinical research, the heroes of the battle are the volunteers.

In the world of clinical research, just as in Narnia, each individual patient makes his or her significant contribution to a whole.

This world is being rapidly transformed by technological developments, as progress allows closer and closer access to research subjects. Innovation in the field of clinical research is therefore indispensable.

Although it is true that the new trends promise a patient-centered vision, we face a new challenge to ensure that these different tools truly treat the patient as a person, and not as an object at the disposal of thirdparty interests. There is a risk of complying solely with the formalities of the legislative framework, shaped by public policy, respecting basic guarantees such as voluntary participation and confidentiality, but no more than that. It is not only a matter of empowering the patient by facilitating and rendering more comfortable his or her interaction, in order to obtain data. The really important thing is to place the patient at the center of our activities and decision, not simply as an object of study, but rather as a human person, with all that that implies, from a philosophical and anthropological standpoint, avoiding any hint of superficiality in proper clinical practices: â&#x20AC;&#x153;Clinical research must view the patient as a rational-person-subjectâ&#x20AC;Śâ&#x20AC;?1

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Even as science and technology are inevitably developing in the field of clinical research, ethics help us to understand scientific knowledge in terms of its final ends, without seeking to dominate it, with the coldness and meanness of the White Witch in Narnia.

Progress in that direction will allow us to arrive at a humanized clinical research, but only if we stop viewing ourselves, the researchers, as the protagonists. We must allow the patients to shine as the true heroes of the story.

Gustavo García-Cardona and Fabio Alberto Garzón-Díaz (eds.), Bioética e investigación científica: la protección de la vida, un compromiso ético y científico (Bogotá: Universidad Militar Nueva Granada, 2002).

2 Roger Verneaux, Filosofía del hombre. Curso de filosofía tomista (Barcelona: Herder, 2002).

3 See C. S. Lewis, The Lion, the Witch and the Wardrobe (London: Geoffrey Bles, 1950) [the first book in the series entitled The Chronicles of Narnia].

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From this perspective, we can conclude that the battle in clinical research is not a combat between ethics and technological progress.

On the contrary, both are strictly necessary: without either one of them, there could be no scientific knowledge that benefits humankind.

“Knowledge, in general, is the result of the relation between subject and object, between consciousness and the world, between thinking and being.”2 The struggle to be waged is that of defending the basic ethical principles of science against bad practices and interests that fail to take into account the central participants.

Because in Narnia, while the White Witch seeks her own benefit, Aslan gives his life to save one of the protagonists, thereby demonstrating consistently that, when one is for oneself, one is also for all the others3.

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HUMAN BEINGS, ETHICS, AND CLINICAL RESEARCH Dr. Jorge Laureano Eugenio

Researcher of the Secretary of Health Jalisco.

Dra. Elisa Gil HernĂĄndez

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Advisor and promoter of research at the Secretary of Health Jalisco.

Clinical research has been consolidated as a basic means of responding to the global health problems that affect humanity, identifying a range of actors in the continual search for drugs to alleviate diseases that do not yet have cures, for vaccines to prevent new and emerging pathologies with high morbidity and mortality, and for nonpharmacological treatments to treat or palliate other illnesses. But in this pursuit, which involves diverse private and collective interests, the incorporation of human beings in the processes forces researchers to perform constant critical self-reflection, which is mirrored in their actions and decision-making.

A first element for reflection is how to render researchersâ&#x20AC;&#x2122; thinking and acting fully conscious, acknowledging actual practice in Mexico and other underdeveloped countries. This has led to arid and contradictory discussion, owing to diverse factors that condition the development of clinical research.

The most delicate matter remains the fact that there are still no clear and concrete mechanisms to ensure that the ethical assumptions established on various levels regarding the participation of human beings in research have permeated activity in the field.

Apart from the benefits of research for participants, the scientific community, and society in general, there are still prejudices that can condition the wellbeing and quality of life of those involved.

Viewed from the perspective of human participants in the research, various motives can be identified: the desire to cure or palliate their diseases, to prevent new illness, or to prolong their lives with quality. It is unfortunate that, for some researchers, these desires are used for the purposes of experimentation and in order to obtain social, economic, or institutional recognition, without due importance being given to the scope and safety of the research, the physical integrity of the participants, the emotional context of their involvement, and its relation with society.

In considering the integrity of human beings who participate in clinical trials, the epistemological vigilance of the researchers is of enormous relevance, this being understood as a process whereby they

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constantly view themselves critically, examining the effects they themselves may have on the trials, the different forms of relationship in play and their impact on the participants, and their own discourses, interpretations, and behaviors, among other aspects.

All this is important to ensure that they do not incur in ethical, legal, or methodological inconsistencies during the course of the research.

For the National Commission on Bioethics in Mexico, informed consent is a process whereby an individual, after receiving the necessary information, makes a voluntary decision to participate in a clinical trial or not to do so. The same institution emphasizes that informed consent is recorded by means of a document, signed and dated, and that it consists of two parts,

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This surveillance is developed mainly within the relationship established by the researcher with the object of study and the participants of the research, and goes beyond the necessary rigor in the correct application of techniques. It also involves a constant review of oneâ&#x20AC;&#x2122;s ontological position in the operative field, that is, the question of when exactly one ceases to be a health worker and becomes a researcher.

Likewise, there is the consideration of when the human being ceases to be a patient and becomes a â&#x20AC;&#x153;research subject,â&#x20AC;? putting at risk adherence to one of the most important ethical postulates established in the health sciences: the free autonomy of clinical trial participants.

The second element of consideration is informed consent, an element of tangible expression of respect for the autonomy of persons not only in the field of health care, but also in that of medical research. Informed consent is not simply a document, but rather a continuous and gradual process, beginning with the first steps in explaining the intentions and objectives of the study. It is an opportunity for reflection and for the potential research participants to inform themselves, corroborate their knowledge, and resolve doubts regarding the manner of their participation, the processes to be undertaken, the possible effects and treatments to be developed as a result of the research, and the consequences of the signatures of both participants and witnesses. Thereafter, it is important to maintain vigilance regarding the fulfillment of what has been agreed on.

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in the first of which information is provided about the proposed research, and in the second of which the research subject formally accepts, by means of his or her signature, to participate in the research.

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The use of informed consent in research merits reflection and analysis, with special attention to particularsituationswhereitmaybemoredemanding than usual: working with minors or incarcerated persons, experimentation on people with serious mental illness, the involvement of unconscious patients, and particularly issues concerning research with women (owing to the permanent discrimination

they suffer in many countries, as well as to the possibility of their being pregnant).

Informed consent must also ensure that explanations have been clear, without any doubts or misunderstanding about the procedures to be performed, as for example the taking of biological samples, the photographing of private images or of certain lesions, the evolution of certain dermatological pathologies when new treatments are applied, video recordings of new surgical techniques, voice recordings, or interviews about experiences with new pharmacological

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management, among others. It is common that, once a process is underway, researchers begin investigating other elements that were not considered at the beginning.

Research subjects should not only have an understanding of the procedures to be performed, but also of why they are performed and how they are managed, as well as safeguards regarding the use that will be made of them in the future, the time spans involved, and the identity of those who will be responsible for these matters. In relation to images and/or photographs, they should also

know how many images will be taken and how their own personal integrity and identities will be protected in the process, whether the images are going to be exhibited or shown (and in what medium: poster, magazine, slide show, etc.), and, in some cases, how long this will be the case.

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In order to render possible the fulfillment of the two assumptions we have analyzed, their application and understanding must begin with educational institutions, in the training of human resources for health, comprising all the disciplines related to the attention of living beings. This will allow professionals to acquire an understanding of and consideration for the well-being, personal integrity, and integral health of the research subjects, apart from any scientific progress that may be expected from a clinical trial. In this way, the incorporation of human beings in clinical research will be based on constant critical selfreflection on the part of researchers and the quality of their research will be guaranteed, insofar as this is possible, by respect for the dignity and human rights of the research subjects.

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PATIENTS HAVE IT RIGHT Thor Nissen

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Doctor, graduate in Clinical Pharmacology and MBA in Quality Management. He has managed to collaborate for the development of medicines in world leading pharmaceutical companies both in medical matters and in clinical research in new drugs, regulation, marketing and sales departments.

Good clinical practice emerged to put patients’ safety above any other objective in clinical research. Yet, until recently, patients were not part of the decision makers in the design of the clinical development programs, traditionally looked through the lens of scientists, primarily focused on a mechanism of action. Anyone working in clinical research can acknowledge patients always stated their feelings on the way protocols and tested treatment options accommodated their needs or not. But their voices were like shouting into an echo chamber. Sponsors, clinical teams, site staff, and other professionals have heard hundreds of conversations from trial “subjects” but hardly incorporated their input in presenting the case studies and insights to decide real actionable takeaways. There is a need and an advantage to acknowledge trial participants as people, with a disease or condition being explored, eager to contribute, and to get involved in the workstreams. “To better design our trials, research questions and the outcomes studied must be prioritized by patients. To more efficiently recruit, retain, and ultimately deliver clinical trials we must understand the patient perspective.”1 We need patients’ perceptions not only to better design trials but also to be better prepared to characterize and support new drugs for health authorities and payers.

Patient centricity journey started at the end of the road. It became obvious that registered drugs and devices that didn’t fit patients’ needs or imposed unbearable burdens were doomed to fail. Patient centered care brought patient judgment to the top of the decisionmaking process. Knowing patients’ main reason for the visit, concerns, and need for information emerged as vital. Diseases signs and symptoms happen in particular patients with individual emotional needs and life issues. Treatment compliance improves when management is mutually agreed upon. And the relationship between the patient and the doctor is enhanced.2 Evidence of patients’ valuable contributions sneaked into clinical research. Patient reported outcomes have been a common tool integrated into clinical research for a long time now. But “the patient’s perspective is often overlooked or poorly described in the

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development of PROMs.”3 This is changing.

For example, The International Consortium for Health Outcomes Measurement included in their international working group of experts and researchers, patient representatives to define a standard set of outcomes and riskadjustment variables.

Making patients partners throughout trial design will help to diversify trial participation, increase retention, and improve compliance among other positive effects. Scaling patientpreferred research and considering patient burden, will result in better-designed products with preferred efficacy.

Drug development should be flooded by likeminded peers who believe in the importance of the patient voice and active participation.

“Finally, to better characterize the benefits and risks of our products for health authorities, we must understand how patients perceive the burden of the disease and the standard of care.

Patients play the most important role in clinical trials, and therefore are in a position to help make a difference.”4 The earlier we bring patients into drug development, the better treatment options will improve in speed, cost, and quality.

Rosseti, L. Patient Centricity is Essential to Modern Day Drug Development. IFPMA News Center. 2015 Mar 23. https:// www.ifpma.org/science-matters-centre/patient-centricity-isessential-to-modern-day-drug-development/ 2 Steward, M. Towards a global definition of patient centred care. BMJ. 2001 Feb 24; 322(7284): 444–445. doi: 10.1136/bmj.322.7284.444 3 Peeters G, Barker AL, Talevski J, et al. Do patients have a say?

A narrative review of the development of patient-reported outcome measures used in elective procedures for coronary revascularisation. Qual Life Res. Published online 2018. doi:10.1007/s11136-018-1795-6 4 Rosetti, L. op cit 1

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Patients’ participation in medical events is also increasing. Every day more, patients make up a substantial part of the speaker faculty.

Their contributions in presentations, panels, and roundtables are being more and more appreciated. Patients’ presence, optimize the integration of their insights in program design, improve relationships, drive improved health literacy, and ultimately, transform outcomes.

Derived from the present pandemic, virtual communications have rapidly evolved and even technology skeptical persons, have had to dive into the Information and Communication Technologies (ICT) world. It may be an opportunity to advance patient-centricity evaluating how it has progressed during the crisis. It is a chance to include patient insights and best practice learnings into re-emergence strategies. Think about how digital support programs can be designed for and with patients. Revolutionize patient outcomes so patient voice can be elevated at every step of product development. This approach needs to comprise every stakeholder in the process as illustrated below

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BIOE THIC AL AND HUMAN RIGHTS CONSIDER ATIONS IN THE SELEC TION PROCESS FOR HEALTH C ARE FOR PATIENTS WITH COVID-19 Dr. in C. Tonatiuh González Heredia Coordinator of the Doctorate in Multidisciplinary Health Research, Research Professor “A”, University Center of Tonala, University of Guadalajara

Mtra. Patricia Elizabeth Silva Colunga B.A. in Marketing, M.A. in Occupational Health Sciences, Ph.D. student in human rights. University Center of Tonala, University of Guadalajara.

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Summary This text aims to reflect on the importance of the role played by bioethics and human rights in the selection processes for health care, in terms of critical hospital medicine, for patients suffering from SARS-CoV-2, or Covid-19. To this end, philosophical, theoretical, and empirical elements are taken from various online sources in the areas of the social sciences and health economics.

The essential importance of the right to health is undeniable, and manifests itself in two aspects: the individual and the social. In spite of being an absolute right, however, its exercise and enjoyment depend on the general conditions of society (Varela & Sotelo, 2000).

In the case of human rights, the right to health corresponds to second-generation rights, which refer, according to Mexico’s National Human Rights Commission, to those “inherent to human nature, without which one cannot live as a human being” (CNDH, 1992).

Supported since 1946 at an international level by the World Health Organization and also figuring in the Mexican constitution, where one of its main characteristics is nondiscrimination, the right to health is considered both a good and a universal value, as well as an inalienable and non-renounceable right, which the government is required to ensure.

This approach is not alien to bioethics, which places the human being at the center

of universal interest in medical practice, whose main principles include autonomy, beneficence, non-maleficence, and justice.

“In global terms, bioethics has positioned itself as an inter- and multidisciplinary task that promotes an integral approach to health, in order to address the tensions and conflicts derived from the clash of values among cultures, weighing both individual and collective interests and emphasizing the protection of groups in conditions of vulnerability” (Secretaría de Salud, 2020).

In the case of the current global health crisis caused by Covid-19, and according to the Bioethics Guide for the Allocation of Limited

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On 12 March 2020, an official declaration of the Covid-19 pandemic was made in Mexico, indicating that the management of the pandemic would be carried out under the guidelines of bioethics. Subsequently, on April 30th, the aforementioned Bioethics Guide for the Allocation of Limited Resources for Critical Medicine in Emergency Situations was published. Its objective is to constitute â&#x20AC;&#x153;a bioethics guide to provide criteria guiding triage decisions when a public health emergency generates demand on critical medicine resources that cannot be met.â&#x20AC;?

Currently, there are approximately 35 million confirmed cases of Covid-19 in the world, and more than a million deaths: figures that exponentially exceed the number of doctors, hospitals, and supplies per person in the world. This has led governments to take drastic measures with respect to medical

care. In some cases, the bioethical decisions forced on governments and health authorities with respect to the dignity of infected patients have been questioned.

Mexico has not been exempt from this emergency, with close to 80,000 deaths, hundreds of thousands of infected people, and scarce resources to face the challenge.

Although the official information provided by the Mexican government refers to control of the disease, whose indicators include the number of hospital beds occupied and the number of active cases, the veracity of the data has been questioned, as have government strategies for addressing the emergency through the public health system.

There has been little clarity regarding bioethical positions and human rights.

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Resources for Critical Medicine in Emergency Situations, issued by the Mexican Ministry of Health (2020), most daily medical practice during a health emergency should be subordinated to the practice of public health, since this is the discipline that has the basic tools to reorganize the entire health field and to confront the emergency in accordance with principles of justice. Multidisciplinary teams of health experts can determine how scarce resources are to be allocated and can prioritize the care of patients who require hospitalization for their critical care, deciding on the selection of patients who should receive care in critical medicine or intensive care, which implies the use of extreme measures to preserve life, given the aggressiveness of the disease. To put this in context, we might note that, toward the end of December 2019, an outbreak of pneumonia in the city of Wuhan (Hubei Province, China) was reported internationally, putting local health authorities on alert, who subsequently confirmed the cause: a new coronavirus (WHO, 2020).

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Without a doubt, we are facing an unprecedented event in modern history, which can only be compared to the great epidemics of centuries past. In our own era, in spite of technological advances, there are doubts and uncertainty about how societies throughout the world are taking radical measures against the pandemic, even though these may threaten human rights, privacy, and ethical standards, especially in relation to the most vulnerable. In the face of these circumstances, it is worthwhile to bear in mind the words of the Director-General of UNESCO: “This crisis demands the best in humanity, with ethical principles as our compass.”

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By Way of Conclusion It is the duty of the Mexican government and health authorities not only to provide individuals with comprehensive health care and the means to address the pandemic, regardless of age, gender, social or cultural background, beliefs, etc., but also to reevaluate the situation derived from this health emergency and to learn from the global crisis, so that alternatives to emergency measures that may violate people’s human rights can be considered, prioritizing human dignity above any other material criteria. This would require that the mercantilist approach to public health becomes obsolete, with the application of the principles of human rights and bioethics to actions related to the health and well-being of the population. Both disciplines must be totally aligned and must be the basis for positioning rights, without which society runs the risk of degradation and involution in the broadest human sense.

References •National Human Rights Commission (1992) Regulations of the

Law of the National Human Rights Commission, Mexico.

CPEUM (1917) Political Constitution of the United Mexican States (CPEUM), Mexico •World Health Organization (1946) Constitution of the World Health Organization.

•World Health Organization (2020) COVID-19: chronology of WHO action, Declaration.

•Ministry of Health (2020) The Bioethics of the COVID-19 Pandemic, National Bioethics Commission. Mexico City, Mexico.

•Fumadó, C. M., Durán, E. L. G., & Morlans, M. (2020). Ethical and Medico-Legal Considerations on Resource Constraints and Clinical Decisions in the COVID-19 Pandemic. Spanish Journal of Forensic Medicine: organ of the National Association of Forensic Physicians, 46(3), 119-126.

•Varela H., & Sotelo G., (2000) Derecho y Salud: Instituciones, Paper presented at the Symposium “Derecho y Salud”, in the module “Institutions”, Instituto de Investigaciones Jurídicas de la UNAM, Mexico, DF.

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SCIENTIFIC E THIC S A S SEEN IN LITER ATURE Humberto Orígenes Romero Porras holds a degree in history from the Universidad de Guadalajara. A former Paralympic athlete (2006-2017), he won a medal at the 2015 Parapan American Games held in Toronto, Canada. A partisan of worthy causes, he is interested in the interconnections between history, literature, and soccer.

Two classic works of English literature have plots that turn on the ethical dilemma of a scientist: Frankenstein; or, The Modern Prometheus (1818), by Mary Shelley, and The Strange Case of Dr. Jekyll and Mr. Hyde (1886),

by Robert Louis Stevenson. In both works, the experiments of a man of science escape his control. Ambition consumes the creator, who is confronted by his own creation.

So important is the connection between the two that Daniel Balderston considers the author of Treasure Island a shadowy precursor of the South American writer.2 The twenty references to Stevenson in the complete works of Jorge Luis Borges, most of them in forewords to various books, bear witness to this devotion.3 In a remarkable tribute to the duality of The Strange Case of Dr. Jekyll and Mr. Hyde, Borges transforms himself into a character out of Stevenson, incapable of distinguishing between one Borges and another.

“Borges y yo” ends with the words: “I don’t know which of the two of us is writing this page.”

About a week has passed, and I am now finishing this statement under the influence of the last of the old powders. This, then, is the last time, short of a miracle, that Henry Jekyll can think his own thoughts or see his own face (now how sadly altered!) in the glass.

Meanwhile, the creation detests his creator, a motif he shares with the monster in Shelley’s novel: The hatred of Hyde for Jekyll, was of a different order. His terror of the gallows drove him continually to commit temporary suicide, and return to his subordinate station of a part instead of a person…

Like Dr. Frankenstein, Jekyll confesses to the crime of having played at being God. Both of them regret the harm their experiments might have done to humanity.

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“I like hourglasses, maps, eighteenth-century typefaces, etymologies, the taste of coffee, and the prose of Stevenson,” wrote Borges in “Borges y yo.”1 The relationship between the Argentinian poet and the Scottish novelist was deep, the latter being described by the former as “a certain very dear friend that literature has given me” in the foreword to Elogio de la sombra.

Stevenson’s tale can function as a detective story, beginning as it does with a lawyer looking into the relationship between the sinister Mr. Hyde and his friend Henry Jekyll, a reputable doctor, whose house has been occupied by Edward Hyde, and ending with Dr. Jekyll’s own account of the events. Jekyll was attempting to create a substance that would separate the evil from the good in each individual. It was an experiment in the spirit of the times,4 Mary Shelley having already dealt with the theme of the manipulation of the spirit as a scientific aspiration. Dr. Jekyll becomes fused with his own creation:

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The Darwin referred to is not Charles, but his grandfather Erasmus, whose experiments in galvanism provided the basis for Shelley’s novel, in which Frankenstein’s monster is brought to life by means of electricity, as the Italian scientist Galvani proposed. The monster develops a deep hatred for Dr. Frankenstein, owing to his condition as an “Adam without a mate,” as José de la Colina5 has put it. The monster asks its creator for a companion, which is created, before being destroyed by the scientist, who immediately regrets his work.

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Shelley’s novel, which actually begins in medias res, with Dr. Frankenstein pursuing his creation across the Antarctic, deals with themes such as good and evil, the fear of solitude, and scientific irresponsibility. Victor Frankenstein, a scientist eager for recognition, joins together fragments of corpses in order to achieve one of science’s greatest dreams: the creation of life. But it all gets beyond his control, for, as the Mexican biologist Antonio Lazcano has accurately expressed it: “Electricity is no substitute for the soul.”6 In El hacedor (1960).

Daniel Balderston, “El precursor velado: R. L. Stevenson en la obra de Borges.” Available online at <http://www.borges.pitt. edu/bsol/dbi.php>.

3 Jorge Luis Borges, Obras Completas (Buenos Aires: Emecé Editores, 1984 [1974]).

4 See the lecture “¡Frankenstein (y la biología)!” by Dr. Antonio Lazcano Araujo, available online at <https://www.youtube. com/watch?v=-UkxZLuPozw>.

5 José de la Colina, “La Mamá del Monstruo de Frankenstein,” Letras Libres (Mexico City), May 2012. Available online at: <https://www.letraslibres.com/mexico-espana/la-mama-delmonstruo-frankenstein>.

6 Lazcano Araujo, “¡Frankenstein (y la biología)!” cited above.

1 2

Illustrated by Fernando Falcone

Will Hyde die upon the scaffold? or will he find courage to release himself at the last moment? God knows; I am careless; this is my true hour of death, and what is to follow concerns another than myself. Here then, as I lay down the pen and proceed to seal up my confession, I bring the life of that unhappy Henry Jekyll to an end.

Mary Wollstonecraft Godwin, who took the name of her husband, the poet Percy Bysshe Shelley, wrote Frankenstein; or, The Modern Prometheus in Switzerland, while travelling in the company of Shelley and Lord Byron in 1818. The title itself contains the metaphor: a scientist who, like the Greek Titan Prometheus, defies the gods. Shelley’s work is in accord with the science of her day: “The event on which this fiction is founded has been supposed, by Dr. Darwin, and some of the physiological writers of Germany, as not of impossible occurrence,” she wrote, in the preface to Frankenstein.

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LÓPEZ-GATELL AND BIOE THIC S IN THE TIME OF THE PANDEMIC Diana Jacqueline Anguiano Castro Graduated in Hispanic Literature from the University of Guadalajara. In 2018 she participated as a speaker in a colloquium held by the same university. In 2020 she took a diplomated in editorial design from the CAAV (University of Audiovisual Media). He works in the teaching area from 2017 to date. Recently, he started to support in several processes about the edition of a next philosophy and literature magazine.

In this way, treatments have been developed in various branches of medicine to help us combat everyday illnesses and diseases. Clinical research goes beyond experimental studies, however, since the roles played by both patients and researchers are of vital importance. It is on this last point that the present text will focus.

Clinical trials were designed to diagnose, prevent, or offer treatments for various illnesses. In some cases, the researchers themselves have served as volunteer subjects in order to learn how a substance functions and what reactions it has on the human body.

López-Gatell Ramírez was born on 22 February 1969 to Dr. Francisco López-Gatell Trujillo and his Mexican wife Margarita Ramírez Duarte, a nurse. His father, born in Tarragona, Spain, in 1925, studied chemistry before becoming a surgeon, specializing in urology, through the Massachusetts General Hospital. Hugo LópezGatell attended the medical school of the Universidad Nacional Autónoma de México (UNAM), graduating in 1994. Six years later he specialized in internal medicine at the Instituto

PROFILE

At different moments in the history of the world there have existed people dedicated to saving lives. People who act only after acquiring knowledge that is typically described as “errorfree.” Which implies that behind every triumph there are countless errors that have been gradually corrected until the desired goal is achieved, to which many minds, bodies, and opinions have contributed.

Over the past year, the health of human beings has been gravely affected by the Covid-19 virus.

In Mexico, a public health expert has undertaken to disseminate the most relevant information regarding the virus, but before the pandemic, he was little known on the international stage and even lacked recognition in his own country, in spite of being a public figure. That has all changed now for this epidemiologist, researcher, academic, and public servant, Hugo LópezGatell Ramírez, who has occupied the post of Under-Secretary for the Prevention and Health Promotion since December of 2018.

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PROFILE

Nacional de Ciencias Médicas y Nutrición Salvador Zubirán and then, as if that were not enough, earned a master’s degree in medical, dental, and health sciences at the UNAM and a doctorate in epidemiology at the Bloomberg School of Health at Johns Hopkins University. As part of his post-doctorate work, he carried out a study of the effects of tuberculosis on the survival of men infected with HIV, which was published as an article in 2008. As a researcher, he has written or participated in the writing of more than forty articles. Over the past year, his work has been cited some 5,000 times and, following his fine performance combatting the pandemic, he was elected to the expert committee to draw up the International Health Regulations of the World Health Organization, on which he will participate for a period of four years.

Several months ago, López-Gatell mentioned the importance of finding subjects for future clinical research to be performed in developing a vaccine against the Covid-19 virus. In a communiqué, the under-secretary emphasized the point that people were at no risk of harm from the testing, as there are international norms, which Mexico of course adheres to, in the areas of biosecurity, protection of human subjects, research standards, and ethics. He also pointed out that anyone, regardless of his or her nationality, could volunteer for the testing, always providing the decision was to do so was made freely. The request for volunteers implied no risk, however, since the health and safety of the participants were to be cared for. In fact, Dr. López-Gatell acts only as a spokesman, since, in line with the aforementioned safeguards and however reluctantly, official notification was given by the Under-Secretary for Health that the testing has been suspended, owing to the detection of certain adverse effects in several subjects. It is still not known whether these were caused by the vaccine itself, but the clinical trials were suspended.

In Mexico, research into any clinical protocol undergoes a rigorous review, before testing, by three committees: ethics, research, and biosecurity. Also, in order to reduce any possibility of causing harm to a minimum, a series of ethical principles has been established to govern the research protocols: respect for personal autonomy, non-detriment, benefit, and justice. These principles, reflected in both Mexican and international guidelines, are of course not limitative in scope, and it is necessary to complement them with other specifically ethical aspects of research, such as scientific integrity, confidentiality in the handling of information, and the social value of the research.

Finally, López-Gatell has indicated that a meeting was held with representatives of Landsteiner Scientific, with a view to collaborating with the Russian government to perform tests of the Sputnik V vaccine in Mexico, in line with the bioethical requirements in effect in Mexico. The future remains uncertain, but it is hoped that the testing phases of the vaccine will soon be complete, so that simple “trial and error” can be left behind for good.

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THE ORIGINS OF QUANTUM PHYSIC S José Luis Romero Ibarra graduated with a PhD in physics from the Universidad de Guadalajara. He did post-doctoral work at the KTH Royal Institute of Technology in Sweden, and has held research fellowships in Concepción, Chile, and Rostock, Germany. In the course of his academic career, he has taught mechanics, electromagnetism, and quantum physics, among other subjects.

The phenomenon of magnetism has been known for a very, very long time, since before the advent of capitalism, or even the Middle Ages, before feudalism or the development of aristocracies.

The word magnetism evokes many things for us in these postmodern times we live in. There are those, for example, who perform New Age therapies with magnets, and perhaps some of us still think of that German doctor whose last name was Mesmer. Not to mention “coaching.”

But there is yet another perspective that tends to bring the concept closer to us.

Without the existence of this bipartite field, it would be difficult to live: it’s as simple as that. Take light, for example. It doesn’t matter whether it’s red, green, or white: it’s always an electromagnetic field. We are also familiar with electric fields functioning alone, as on those dry days when we find ourselves giving “shocks” to other people. Magnetism, moreover, is what helps us keep the fridge door closed (there is a magnet in the strip of plastic that runs around the frame of the door).

Without an understanding of magnetism, it would be impossible to build a television, or to have perfected its functioning, from cathode ray tubes to LED screens. Neither would we have computers, nor the cellular telephones that allow us to send messages, listen to music… or date online.

GADGETS

The development of technology over the past century would have been impossible without magnetism, and technology would be impossible without science. It is this scientific perspective that we sometimes fail to consider. In the case of magnetism, let us remember that it is seldom found alone: it tends to go hand in hand with electricity. In physics, magnetism is a result of the existence of a magnetic field, just as electricity is that of an electric field. Since they are so often found together, however, we generally speak of electromagnetic fields.

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GADGETS

Physicists have been studying magnetism and electricity throughout the ages, but it was in the nineteenth century that the greatest progress was made. This was due mainly to two British scientists: Michael Faraday and James C. Maxwell. They were able to bring together the findings of other researchers and contribute new ones of their own, ordering them and synthesizing them into the four laws, known as Maxwell’s equations, according to which the entire theory of electromagnetism is now studied.

Thus, in the nineteenth century, there was already a scientific basis for describing electromagnetic fields and for using their properties to develop technology.

Toward the end of the nineteenth century, however, something happened: an experiment that failed to fit the theory. Questions arose; doubts were kindled. Everything was reviewed, the experiment was redone, all the details were carefully monitored, and the results came out the same. Proposals were made to modify the theory: some aspects were improved, while others were thrown out. Option after option was considered, but nothing quite fit.

It was the colors that were responsible. As simple as that, right? Green, orange, brown, purple, white, violet, yellow, blue, vermilion, fuchsia… And what about black? The only truly guilty party was a blackbody. This was what had left the scientists unable to understand what was happening.

It was known that, if a body is illuminated with white light, it appears as yellow to our sight, because only the light of that color is reflected, whereas all the rest is absorbed. The same thing

happens if we illuminate a blue object. We see that a bottle of red wine is green because only the green light is reflected to our sight, while the other colors are absorbed. But what happens if we have a blackbody? What is a blackbody in physics?

Imagine a sphere, of iron perhaps, that has been hollowed out so that only the shell remains. If we pierce a hole in it and then heat it, we will see that the sphere turns red, like a burning coal or a needle placed in a fire.1 In other words, it emits light (it radiates). The hole allows us to observe what is happening inside, because of the radiation that comes out. Since the cavity also emits light, we can see what there is inside. Could a star be conceived as a sort of blackbody?

Max Planck took a little step further. Just a little step, but one that overturned everything, explained everything, determined, mathematized, revolutionized, conceptualized, and founded everything: indeed, it founded quantum physics. For that little step, Planck was awarded the Nobel Prize in 1918, “in recognition of the services he rendered to the advancement of Physics by his discovery of energy quanta.”2

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Humanity had not realized the existence of this phenomenon because it happens only in the “micro-world,” in the world of things we cannot see with our eyes, of phenomena that do not appear in everyday life. The term quantum generates curiosity, a premonition of boredom, and even a great deal of extravagant nonsense, spoken as it is with the penetrating gaze of the savant, in an atmosphere of genius, applied to many things beyond its true scope.

It was not long before Planck proposed the quantization of energy, so that other quantum phenomena might be discovered experimentally and a theory be formulated.

The theory is disconcerting when encountered for the first time, but once we have mastered it, it can be used in the development of new technology. One thing is for certain: in the course of more than a century now, the study of quantum physics has taken some great leaps forward.

1 D. Halliday, R. Resnick, and K. S. Krane, Physics, vol. 2 (John Wiley and Sons, 2002).

2 <https://www.nobelprize.org/prizes/physics/1918/summary/>

THE SMART DEC ADE Mauro Orozco Moreno He is a communicologist from Univa and a historian from the University of Guadalajara. His professional experience includes teaching, advertising and journalism. He is co-founder of the website Operación Gamer, in which since 2018 he is dedicated to video game journalism. He has collaborated with portals such as Level Up o XatakaMX.

We are living at a time when what we used to think of as “science fiction” is now the science we are familiar with every day. All those things that authors like Philip K. Dick (whose novel inspired the legendary motion picture Blade Runner) or William Hanna and Joseph Barbera (with The Jetsons) used to dream about (or, in some cases, fear), from the 1960s through the 1980s, we now see all around us in our everyday lives. Some of the common

electronic devices we use have fulfilled the dreams of Bruno Bianchi, when he created Inspector Gadget, except that they are contained in a smartphone, rather than a cyborg police detective.

In the fields of science, medicine, and engineering, technology has progressed

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But the quantization of energy is as if there were only squares of chocolate of exactly 500 calories. As if we could eat one square, or two, but never leave half of one, or a third, or any little bit of one. We could also eat ten, but only if we’re sure ingest them entirely, however cloying or unhealthy that may be! And the same applies to the production of the squares of chocolate: only whole squares could be produced in the factory, with no possibility of producing packages of half-squares. If the packaging says 500 calories, that’s what it has to be. In the end, a hundred squares might come out of the machine, or 261, or 593, or

as many as you choose, but they would all be whole squares, with no fractions. To return to energy, we can say it comes in whole squares or, to use the language of physics, in quanta.

To put it another way, energy is quantized.

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We are coming to understand that this concept of “smart” has to do with making a device as multifunctional as possible. Can a laptop computer be even smarter than it is?

Well, Asus has come up with a way for its devices to multitask, using double screens.

On the one hand, we have the Asus VivoBook

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to limits we could only have imagined once, as we left the movie theater after having seen Terminator.

Robots and advanced artificial intelligence are a reality now, equipped with tools that make their jobs easier for many people working on behalf of the wellbeing of society. But there are other kinds of technology. What about all that domestic technology, the kind we use every day at home, in our cars, or at the gym?

We are coming to the end of a decade marked mainly by the appearance and use of smartphones and social media, and everything seems to indicate that the next decade will continue in the same direction. The fact that the present decade is ending with devices such as “smart TV” and “smartwatches” suggests that a “smart decade” is on its way.

What else could be “smart”? A good example of what we can expect to see over the next decade is Huawei X Gentle Monster Eyewear, a kind of “smart sunglasses.” These Huawei sunglasses are hands-free and equipped with stereo sound and 128-millimeter loudspeakers.

They can be manipulated by touch along the sides, in ways that can be personalized, using AI Life apps for Android and Eyewear for iOS. For example, a call can be answered by tapping on the left side of the glasses, or the volume can be adjusted by sliding a finger forwards or backwards along the right side.

https://www.xataka.com/ordenadores/asus-rog-zephyrus-duo-15-caracteristicas-precio-ficha-tecnica

S15, whose trackpad can be converted into a touchpad. The idea is that the touchpad can perform certain secondary tasks. For example, if the user is working on a document in Word, the browser can be opened on the touchpad, perhaps to change a song on Spotify, or to make shortcuts for commands likes Copy, Paste, Italics, or Bold. In this way, the user does not need to be constantly opening and minimizing windows: it is simpler and faster to be able to do several things at the same time.

But Asus has taken this concept to an even higher level with its Zephyrus Duo 15. In this case, the touchpad is much larger, so the tasks

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performed on it can be much more complex.

For example, the user can be on a video conference on the main screen, while at the same time working on a document or reading something on the secondary screen.

The brand, however, that is taking the concept of “smart” the farthest is definitely Xiaomi, with its Xiaomi Ecosystem. What is this ecosystem? According to the Chinese brand (and not to get bogged down in details), it is a series of up to 2,000 everyday household products, from lightbulbs to skateboards, and including coffeemakers, pressure cookers, stoves, air purifiers, televisions, security cameras, scales, and many others. https://www.tuplaystation.es/wp-content/uploads/2020/11/con-ps5-xbox-series-x-esserci-passaggio-definitivo-digitale-v3-460691-1600x900-1.jpg

https://www.xiaomiadictos.com/wp-content/uploads/2020/06/comprar-productos-gadgets-xiaomi-china.jpg

This is the decade that is awaiting us. And we haven’t even looked at some technology that already exists ―and that raises ethical and moral issues―, like Elon Musk’s Neuralink, which basically tries to make our brains themselves a little “smarter.” Perhaps we are closer than we think to that day when we can charge our cellphone by leaving it out in the sun (Apple’s ecological proposal for its iPhone 12) or when we don’t have to worry about running into someone vaguely familiar on the street and having nothing to say (thanks to Neurolink, which will bring up data about the person through facial recognition). Our own moral compass is the only thing keeping us from entering into a cyberpunk scenario, because within the next decade all this technology will be within our reach, on the shelves of the nearest department store, or ― to stay in the same mood― two or three clicks away on Amazon.

GADGETS

Another common household device that tends to make use of the latest technology is the videogame console. And the new decade begins in fact with a new generation of both Xbox and PlayStation consoles. The interesting thing about these new devices is that they are no longer designed just for playing: we are able to see things in much greater detail, down the pores on the face of Geralt de Rivia in The Witcher 3, played by Henry Cavill in the Netflix series. These new consoles are conceived to be the entertainment center of everybody’s rec room.

We can watch Blu-ray movies on them and even stream content such as Netflix, Amazon Prime Video, and the brand new Disney+. In the future, we can just leave all our home entertainment needs to Xbox Series X and PlayStation 5.

All of these devices can be connected by Bluetooth, through the Xiaomi Home app, to your smartphone and manipulated from it. So whether it is a matter of adjusting the brightness of a lightbulb, getting notification of when the rice is ready, keeping your home safe with security cameras, seeing how far you went on your skateboard, or checking your body water percentage on the scale, Xiaomi makes everything “smart.”

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EDITION INQUIRY What is your main concern about health and ethics?

EDITION INQUIRY

Dr. Ana Luisa Caballero Elvira Along the history we have seen different atrocities made to the humanity in favor of the medical science and health, nevertheless, it is not different what we are living at the present time in countries considered of the third world, where the poverty abounds, where the medical attention is expensive, or they do not have the form to accede to her. The population has to look for different options to have medical attention, that is why, during the development of new drugs, where free invitation is made to participate in the protocols, many times the vulnerable population can or has come to lie in their medical history putting in danger their life and the integrity of the doctor. It is thanks to the independent Ethics Committees, which have been given greater autonomy and have opened up new possibilities for analyzing this type of situation, that we can go to the site in question to supervise the processes, without forgetting that in the informed consents patients are reiterated that they can speak to us if they have any doubts about their rights.

Dr. Arieh Roldán Mercado Sesma In practical terms, my main concern is that these two aspects and the economic factor are mixed. When ethical aspects are not considered during the practice of some health care provider, this action affects the health of another person in any of the spheres of his life, it could be in a reversible or, in the worst case, irreversible way. Most health decisions

are made considering only the perspective of one person or a few, without considering the user or patient, and many times without any evidence that the ethical aspects have been discussed, since most of the time the economic aspects are more relevant.

Dr. Thor Nissen Health and ethics are supposed to walk together, inseparably. Where to draw the line between them, may become tricky. Particularly in health research where unconceived chapters of the past have, willingly or not, darkened this discipline. The worst mistake we can make is to believe that these aberrations cannot happen again. We must keep our eyes, and mostly our consciousness, open. Before answering the question: How far am I capable to go to answer a scientific question? I invite you to review Milgram’s experiment, also identified by “The Perils of Obidience”, title of the article where the author first published the results and his conclusions. The experiment has been replicated many times with similar consequences. Those who want and can take 10 minutes, may watch the following related video: https://www.youtube.com/ watch?v=iUFN1eX2s6Q.

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THE AUTHOR A S ANTHROPOLOGIST Bruno Cayetano Pérez Munguía Anthropologist trained by the University of Guadalajara. Professor of social sciences in high school and consultant in social research applied to companies.

To understand the concept of the author as anthropologist, and not as Geertz proposed, it is necessary to remember that the social sciences have struggled since their first attempts to position themselves as “hard” objective sciences” sciences, polishing their models, methodologies, terms and discourses. The use of language was restricted in order to “faithfully” use specific terms to represent phenomena.

Analytical philosophers tried (and some still

do) to understand and describe the world from logical formulas and truth tables.

Sociology proposed a statistical approach to understanding social acts. Moreover, it should be added that most of it was done from the Western discourse.

It is not everything lost; on the contrary, the openness of the social sciences has changed and allows entry to all those things that should never have been expelled. Linguistics and its

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The thick description that becomes into ethnography is the main material of the anthropologist who tries to describe, in the most detailed and “objective” way possible, the reality of a community, phenomenon or culture. The main material is the representation of what has been seen or lived in broad texts that give account of every social nook. Clifford Geertz in The Anthropologist as Author vindicates this work by making the difference between “being there” and “being here”, referring to “being there” as observing and noting and “being here” as writing and interpreting. The social scientist, then, resembles a novelist who draws with words, well searched and stilted, avoiding inappropriate or biased uses, since every scientist should move away from subjectivities to better representation of reality.

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development within the social sciences has allowed part of that change. Understanding how language and its internal structures work and how they relate to corporeality, representation, and perception, allowed that openness. Linguistic relativism and latest generation semiotics are nothing more than that openness. That is, the theories that argue that the ways of perceiving and the needs of subsistence given by the environment are reflected in the type of words -of necessary concepts- that are used to name the world and, in turn, these reorganize reality by being filters of the environment. We can see this through the theories of anthropologist Edwar Sapir and linguist Benjamin Lee Whorf or all the fourth generation semiotists.

The vindication of the author as anthropologist comes here. Geertz used to say that the anthropologist acted as a writer, but this is only true as the sciences have taken it away part of their work from writers without due recognition. There is a branch in anthropology called Ethnoliterature, which is nothing more than anthropology done as poetry, stories, novels, and narrations. Geertz knew it and many others after him, but they still were the ones who put the realities of others into their words.

In order to be as accurate as possible to reality, a key informant is used, which is the one who can guide the explorer through every corner of his culture so the anthropologist can describe it. But what would happen if the key informants themselves do this work?

Then we would have ethnoliterature. What if that ethno-writer was a poet? Well, the writings would be plagued by the visions of the culture, with its metaphors, its feelings, and its corporeality in words and in graphic forms. Here we could mention Juan Rulfo, whose writings are a representation of rural Mexico; which are catalogued as fantasy or a combination between reality and fantasy. If a Jewish-Christian informant mentioned to us that after death there is a reincarnation on a divine plane, would we consider it a fantasy?

Would we think that what he tells us is a mixture of reality and fantasy or would we accept that it is part of his way of interpreting the world, and knowing and feeling himself?

That story is real insofar as it is an expression of his way of facing the world. The decisions he makes will be based on his conception and that does not make it any less real. “A philosopher is only a philosopher when he philosophizes”, said Manuel García Morente.

Fantasy will only be fantasy when we see it like that.

Ethnography can be done from literary, poetic, and narrative writings. A writer can be an anthropologist whose key informant is him. The naturalistic works of literature are a great example of this. Authors like Federico Gamboa express in their lines the reality of their time and they are dense descriptions that illustrate with words the environment, the forms of life, hierarchies, and power relations, to mention a few. Literary writings are body and culture projected in signs; they are symptoms, signs, of our environment.

Literature is culture made flesh, made letter, and a good author is a great anthropologist.

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The graphic form of a language is also part of the interpretation of the world. As an example we could put the kanjis (Japanese writing) that in their lines draw the objects and sounds represented. The kanji for person is the abstraction of the human figure in two lines that cross and form a stick with two legs or just the two legs (人). In the kanjis is the body itself, reality itself, and in the writings that may arise from them as well. Words with all their connotations are part of the culture and are impregnated with corporeality, feelings, and emotions, even graphically. This is how writings go beyond literary figures.

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