Medicines and vaccines have transformed the prevention and treatment of diseases. In addition to their benefits, medicinal products may also have side effects, some of which may be undesirable and/or unexpected.

For example, thalidomide was introduced in the late 1950s as a sedative and a treatment for morning sickness in pregnant women. By the early 1960s, reports began to emerge of severe birth defects associated with its use, including phocomelia, a condition characterized by the malformation of limbs. The thalidomide crisis resulted in significant human suffering and marked a turning point in drug regulation. Thalidomide was sold in over 46 countries, with the highest number of cases reported in Germany, the UK, Canada, and Australia. It’s estimated that around 10,000 babies were born with thalidomide-related birth defects worldwide. These numbers underscore the profound impact of the thalidomide crisis on public health and drug regulation. The crisis prompted significant changes in drug regulation, leading to the enactment of stricter testing and approval processes, such as the 1962 Kefauver-Harris Amendment in the U.S.

All medicines and vaccines undergo rigorous testing for safety and efficacy through clinical trials before they are authorized for use. However, the clinical trial process involves studying these products in a relatively small number of selected individuals for a short period of time. Certain side effects may only emerge once these products have been used by a heterogenous population, including people with other concurrent diseases, and over a long period of time (Figure).

Figure. Overview of investigation into drug safety in the United States.

· Medicines may affect the body in unintended, harmful ways. These effects, called side effects, adverse events or adverse reactions, represent the risks of taking medication. An adverse drug reaction (ADR) can be defined as ‘an appreciably harmful or unpleasant reaction resulting from an intervention related to the use of a medicinal product; adverse effects usually predict hazard from future administration and warrant prevention, or specific treatment, or alteration of the dosage regimen, or withdrawal of the product.’ Since 2012, the definition has expanded to include reactions resulting from errors, misuse, or abuse, as well as suspected reactions to unlicensed or off-label uses of medicines, in addition to those occurring with authorized use at normal doses. Adverse drug reactions have been observed and monitored for many years: In 1937, 107 deaths, many in children, occurred in the United States from the use of a cough syrup that used diethylene glycol as a solvent. This event led to the 1938 Food, Drug, and Cosmetic Act, which for the first time required proof of safety prior to marketing.

· In 1955, over 40,000 children developed abortive polio (51 of whom were permanently paralyzed) and five died from a polio vaccine made by Cutter Laboratories that was not effectively inactivated during manufacturing. The incident also sparked a polio epidemic in the families and communities of those immunized with the defective vaccine, leading to an additional 113 people who were paralyzed and five more deaths. In ensuing law suits, it was determined that pharmaceutical companies could be held liable for harm from their products even if there was no negligence.

· In 1961, more than 10,000 children worldwide were born with severe birth defects (phocomelia) due to in utero exposure to thalidomide, a drug that had been used to treat pregnancy-related nausea. Even though thalidomide had not been released in the United States, this event led to the Kefauver–Harris Amendment, which strengthened the requirements for safety testing and for the first-time required proof of efficacy prior to a drug being marketed. This public health disaster also spurred the development of formal spontaneous reporting systems for pharmacovigilance, which are still the primary method of identifying safety issues in approved medications.

· In the 1970s, it was discovered that diethylstilbestrol caused clear cell adenocarcinoma of the cervix and vagina in women exposed in utero decades earlier.

· In 1984, psoralen and ultraviolet A (PUVA) was definitively linked to an increased risk of squamous cell carcinoma, approximately 10 years after the first description of PUVA therapy for psoriasis. It took over 20 years to establish a link between PUVA and melanoma, which remains controversial.

· Of drugs approved by the US Food and Drug Administration (FDA) between 1996 and 2012, one-third received boxed warnings and more than 40% of these drugs acquired the warning a median time of 4 years after approval.

· Since 2000, many of the prescription drugs removed from the market include classes of medications that are commonly prescribed, such as antihistamines (e.g., terfenadine), nonsteroidal anti-inflammatory agents (rofecoxib, valdecoxib), antibiotics (trovafloxacin), lipid-lowering medications (cerivastatin), and an immunosuppressant for the treatment of psoriasis (efalizumab).

· Between 2008 and 2015, 29% of boxed warnings issued to drugs on the US market were new and 32% were major updates to previous warnings.

· The incidence of adverse drug reactions has remained relatively unchanged over time, with research suggesting that between 5% and 10% of patients may suffer from an ADR at admission, during admission or at discharge, despite various preventative efforts.

· In 2012, McKinsey & Company estimated that the cost of 50 to 100 million preventable, error-related adverse drug events ranged from $18 billion to $115 billion.

It is important to quickly identify new risks or changes to known risks associated with the use of medicines. Timely actions must be taken to minimize these risks, maximize the benefits, and promote the safe and effective use of medicines by patients. These activities are collectively known as pharmacovigilance.

Pharmacovigilance, also known as drug safety, is the pharmaceutical science concerned with the “collection, detection, assessment, monitoring, and prevention” of adverse effects associated with pharmaceutical products. The term “pharmacovigilance” is derived from the Greek wordpharmakon(meaning drug) and the Latin wordvigilare(to keep watch). As such, pharmacovigilance focuses primarily on adverse drug reactions, defined as any noxious and unintended response to a drug, including lack of efficacy. Medication errors—such as overdose, misuse, abuse, and drug exposure during pregnancy or breastfeeding—are also of interest, even when no adverse event has occurred, due to their potential to result in harm.

In recent years, the scope of pharmacovigilance has expanded to include:

· Herbals

· Traditional and complementary medicines

· Blood products

· Biologicals

· Medical devices

· Vaccines

Many other issues are also relevant to the science of pharmacovigilance, including:

· Substandard medicines

· Medication errors

· Reports of lack of efficacy

· Use of medicines for unapproved indications with insufficient scientific support

· Case reports of acute and chronic poisoning

· Assessment of drug-related mortality

· Abuse and misuse of medicines

· Adverse interactions between medicines and chemicals, other drugs, or food

Pharmacovigilance activities include:

• Collecting and managing data on the safety of medicines
• Looking at the data to detect “signals” (any new or changing safety issue)
• Evaluating the data and making decisions with regard to safety issues
• Pro-active risk management to minimize any potential associated risks
• Acting to protect public health (including regulatory action)
• Communicating with and informing stakeholders and the public
• Audit of the outcomes and key processes involved.

The specific aims of pharmacovigilance are to:

· Improve patient care and safety in relation to the use of medicines and all medical and paramedical interventions

· Enhance public health and safety concerning the use of medicines

· Contribute to the assessment of the benefits, harms, effectiveness, and risks of medicines, thereby encouraging their safe, rational, and more effective—including cost-effective—use

· Promote understanding, education, and clinical training in pharmacovigilance, along with effective communication to the public

Information received from patients and healthcare providers via pharmacovigilance agreements, as well as other sources such as the medical literature, plays a critical role in providing the data necessary for pharmacovigilance to take place. In order to market or to test a pharmaceutical product in most countries, adverse event data received by the license holder (usually a pharmaceutical company) must be submitted to the local drug regulatory authority.

Ultimately, pharmacovigilance is concerned with identifying the hazards associated with pharmaceutical products and with minimizing the risk of any harm that may come to patients. Companies must conduct a comprehensive drug safety and pharmacovigilance audit to assess their compliance with worldwide laws, regulations, and guidance.

The activity that is most commonly associated with pharmacovigilance and which consumes a significant number of resources for drug regulatory authorities (or similar government agencies) and drug safety departments in pharmaceutical companies, is that of adverse event reporting. Adverse event reporting involves the receipt, triage, data entry, assessment, distribution, reporting (if appropriate), and archiving of adverse event data and documentation. The source of adverse event reports may include spontaneous reports from healthcare professionals or patients, solicited reports from patient support programs, reports from clinical or post-marketing studies, reports from literature sources, reports from the media (including social media and websites), and reports reported to drug regulatory authorities themselves. For pharmaceutical companies, adverse event reporting is a regulatory requirement in most countries. This reporting also provides data to these companies and drug regulatory authorities that play a key role in assessing the risk-benefit profile of a given drug.

Organizations such as World Health Organization (WHO), International Council for Harmonization (ICH), The Council for International Organizations of Medical Science (CIOMS), and International Society of Pharmacovigilance play a key collaborative role in the global oversight of pharmacovigilance.

The number of National Centers participating in the WHO International Drug Monitoring Program has grown from 10 in 1968, when the program began, to 67 in 2002, and continues to increase. The centers vary considerably in size, resources, support structure, and scope of activities. Collecting spontaneous reports of suspected adverse drug reactions remains their core activity.

In conclusion, maintaining balance in life is essential in all aspects. The usefulness of almost anything can diminish and even become harmful when used excessively. Although medicines play a vital role in healthcare, their effects must be closely monitored to prevent potential adverse events. In addition, with the rapid spread of drug information worldwide—especially highlighted during the COVID-19 pandemic—there is a growing need for routine and timely communication between National Centers and national regulatory authorities. Many regulatory bodies across different regions have established strong collaborations to share safety data, discuss regulatory decisions, and align on policies. Regular dialogue and coordination among National Centers are crucial to ensuring the safe and effective use of medicines.

References

1. https://www.who.int/teams/regulation-prequalification/regulation-and-safety/pharmacovigilance

2. Offit P. The Cutter incident, 50 years later. N Engl J Med. 2005;352(14):1411–1412.

3. Talbot JC, Nilsson BS. Pharmacovigilance in the pharmaceutical industry. Br J Clin Pharmacol. 1998 May;45(5):427-31. doi: 10.1046/j.1365-2125.1998.00713.x. PMID: 9643613; PMCID: PMC1873545.

4. Solotke MT, Dhruva SS, Downing NS, Shah ND, Ross JS. New and incremental FDA black box warnings from 2008 to 2015. Expert Opin Drug Saf. 2018;17:117–123.

5. Coleman JJ, Pontefract SK. Adverse drug reactions. Clin Med (Lond). 2016 Oct;16(5):481-485. doi: 10.7861/clinmedicine.16-5-481. PMID: 27697815; PMCID: PMC6297296.

6. Ebel T, George K, Larsen E, Neal E, Shah K, Shi D (October 2012). “Strength in unity:The promise of global standards in healthcare” (PDF). gs1.org. McKinsey & Company.

Nooriye is a 39-year-old Iraqi female. She had a pretty normal life until a group of terrorists knocked on her door. Her two sons were killed in front of her. She was abused and tortured for days, as was her husband. Rebels eventually took her husband and left. Some neighbors helped her to bury her sons and provided her with shelter and food. She was about to kill herself when, miraculously, her husband came back 57 days later. He never told her what he went through during those 57 days. They were both in extreme pain but able to hold onto each other.

They immigrated to the U.S. a year later. Her husband found a job and is still working. They are safe now, but it has not been enough to heal them. Both still have nightmares and flashbacks. She spends all her time in her home. She stares at walls, feels numb and very fearful, and cries every day. Her speech is sparse, and she never smiles. She goes out with husband once a day but grabs his hand and won’t let him go when they are out. When faced with stress, she often passes out.

Her husband “has to be strong because she is the only thing he has,” although he also has extreme pain. He hides his tears from his wife, is unable to sleep at night, feels guilty, and misses his sons. He is afraid to make any Iraqi friends and stays away from mosques.

Obviously, providing a safe place, food, and a job is not enough to heal these people’s pain. Invisible wounds and problems are much harder to treat than visible ones.

In this article we will try to elucidate some elements of what Nooriye and thousands of other families have been exposed to all around the world.

Mass trauma

When a group of people, regardless of size, experience psychological effects after a trauma that was suffered collectively, this is called a mass trauma. Sometimes an entire society witnesses the same trauma, and this may cause a collective sentiment, often resulting in a shift in that society’s culture and mass actions.^1,2

Wars, political violence, natural disasters, exile, torture, and terrorism are examples of mass trauma. The Holocaust, the Atomic bombing of Hiroshima and Nagasaki, slavery in the United States, and the 9/11 attacks are well-known collective traumas.

Collective traumas have been shown to play a key role in group identity formation. Having the same problems, suffering from the same pain, and being under the same pressures bring individuals together. This togetherness eventually helps to build a community, a group, and sometimes a nation. Almost every nation has traumatic events in their history. Even the concept of “nation” is extensively affected by these events.

Nevertheless, despite its role in building group identity, mass trauma is still individually painful. In fact, the effects of mass trauma can be very deep and transferred through the generations. In 1966, clinicians observed that large numbers of children of Holocaust survivors were seeking treatment in psychiatric clinics in Canada. Moreover, when compared to the general population, the grandchildren of Holocaust survivors were three times more likely to seek clinical psychiatric help.³

Post-Traumatic Stress Disorder

According to the National Center for Posttraumatic Stress Disorder, the most common stress reactions in the wake of disaster may include the following:

Emotional reactions, including shock, fear, grief, anger, guilt, shame, feeling helpless, feeling numb, and sadness.

Cognitive reactions, including confusion, indecisiveness, worrying, shortened attention span, and trouble concentrating.

Physical reactions, including tension, fatigue, edginess, insomnia, bodily aches and pains, startling easily, racing heartbeat, nausea, change in appetite, and changes in other bodily desires.

Interpersonal reactions, including distrust, conflict, withdrawal, work or school problems, irritability, loss of intimacy, and feeling rejected or abandoned.⁴

Several factors present in the acute-phase recovery environment of a disaster have been found to aggravate stress reactions and therefore increase survivors’ risk of developing negative outcomes. These include:

• Lack of emotional and social support
• Presence of other stressors such as fatigue, cold, hunger, fear, uncertainty, loss, dislocation, and other psychologically stressful experiences
• Difficulties at the scene
• Lack of information about the nature and reasons for the event
• Lack of, or interference with, self-determination and self-management
• Treatment [given] in an authoritarian or impersonal manner
• Lack of follow-up support in the weeks following the exposure

Protective factors that may mitigate negative effects include:

• Social support
• Higher income and education
• Successful mastery of past disasters and traumatic events
• Limitation or reduction of exposure to any of the aggravating factors listed above
• Provision of information about expectations and availability of recovery services
• Care, concern and understanding on the part of the recovery services personnel
• Provision of regular and appropriate information concerning the emergency and reasons for action.⁵

In most cases, the symptoms of trauma eventually disappear, but unfortunately, some of the survivors of the mass trauma will eventually develop Post-Traumatic Stress Disorder (PTSD). PTSD is a mental disorder resulting from exposure to an extreme traumatic stressor.

The National Comorbidity Survey Replication (NCS-R), conducted between February 2001 and April 2003 in the U.S., estimated the lifetime prevalence of PTSD among adult Americans to be 6.8%.⁶ The lifetime prevalence of PTSD among men was found to be 3.6% and among women 9.7%. ⁷

PTSD is described in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM 5) which is published by the American Psychiatric Association, as:

Criterion A (at least one required): The person was exposed to: death, threatened death, actual or threatened serious injury, or actual or threatened sexual violence, in the following way(s):

• Direct exposure
• Witnessing the trauma
• Learning that a relative or close friend was exposed to a trauma
• Indirect exposure to aversive details of the trauma, usually in the course of professional duties (e.g., first responders, medics)

Criterion B (at least one required): The traumatic event is persistently re-experienced, in the following way(s):

• Intrusive thoughts
• Nightmares
• Flashbacks
• Emotional distress after exposure to traumatic reminders
• Physical reactivity after exposure to traumatic reminders

Criterion C (at least one required): Avoidance of trauma-related stimuli after the trauma, in the following way(s):

• Trauma-related thoughts or feelings
• Trauma-related reminders

Criterion D (at least two required): Negative thoughts or feelings that began or worsened after the trauma, in the following way(s):

• Inability to recall key features of the trauma
• Overly negative thoughts and assumptions about oneself or the world
• Exaggerated blame of self or others for causing the trauma
• Negative affect
• Decreased interest in activities
• Feeling isolated
• Difficulty experiencing positive affect

Criterion E (two required): Trauma-related arousal and reactivity that began or worsened after the trauma, in the following way(s):

• Irritability or aggression
• Risky or destructive behavior
• Hypervigilance
• Heightened startle reaction
• Difficulty concentrating
• Difficulty sleeping

Criterion F (required): Symptoms last for more than 1 month.

Criterion G (required): Symptoms create distress or functional impairment (e.g., social, occupational).

Criterion H (required): Symptoms are not due to medication, substance use, or other illness.⁸

Treatment for mass trauma:

Treatment for mass trauma should be delivered at two different levels: the community level and the individual level.

1. Community level:

Dr. Frantz Omar Fanon gives the recipe for mass trauma treatment at the community level: “Mass trauma can be alleviated through cohesive and collective efforts such as recognition, remembrance, solidarity, communal therapy and massive cooperation.”

The statement above can be a topic for a separate article. Here, we would like to express the importance of the remembrance days. People comes together on remembrance days and remind the victims that they are not alone and not forgotten. This can be therapeutic for the victims and alleviate their pain.

2. Individual level

PTSD treatment includes pharmacotherapy (medical treatment) and psychotherapy. Some of the medications which have been helpful combatting depression are selective serotonin reuptake inhibitors (SSRIs), such as Fluoxetine (Prozac), Sertraline (Zoloft), Paroxetine (Paxil), and serotonin-norepinephrine reuptake inhibitors (SNRIs) such as Venlafaxine (Effexor) and Duloxetine (Cymbalta).

There are several therapy types that have been shown to be effective at treating PTSD. Trauma-focused psychotherapies are the most highly recommended psychotherapies for PTSD. In these therapy types the treatment focuses on the memory of the traumatic event or its meaning. These treatments use different techniques to help a victim process their traumatic experience. Some involve visualizing, talking, or thinking about the traumatic memory. Others focus on changing unhelpful beliefs about the trauma. Prolonged exposure therapy, Cognitive Processing Therapy, Eye-Movement Desensitization and Reprocessing, Brief Eclectic Psychotherapy, and Narrative Exposure Therapy are the some of the therapies that have been found to be helpful for PTSD patients.

Additionally, spirituality might help treat PTSD, too. A study of Bosnia-Herzegovina war veterans suggested that veterans who prayed had significantly higher levels of incorporation, self-protection, and reactive formation and significantly lower levels of regression, compensation, transferring, lack of control, and aggressiveness than their peers who did not pray. ⁹

In brief, providing shelter, food, and a safe environment are mandatory for trauma patients, but they aren’t nearly enough. Psychological traumas are very hard to treat, and treatment may take years. It has been shown that soldiers who have somebody to share their war experience/trauma with, have a lower risk for PTSD when compared with the ones who can’t talk to anybody. Victims need professional help along with community support. Trauma can be alleviated through cohesive and collective efforts and cooperation. Praying for the trauma victims, as politicians suggested for recent hurricane victims, definitely has some social impact. It has also been shown that medication/prayers decrease PTSD symptoms ¹⁰; however, showing support and empathy, listening to victims, and acts of remembrance are the other key elements of community support.

References

1. Lisa Gale Garrigues, “Slave and Slave Holders Break Free of History’s Trauma“, Yes Magazine, August 2, 2013
2. Updegraff, Silvler, Holman, “Searching for and Finding Meaning in Collective Trauma, Journal of Personal and Social Psychology, September 2008
3. Coffey, R. (1998). Unspeakable truths and happy endings. Sidran Press. ISBN1-886968-05-5
4. https://www.ptsd.va.gov/professional/pages/handouts-pdf/Reactions.pdf
5. NSW Institute of Psychiatry and Centre for Mental Health. (2000). Disaster Mental Health Response Handbook.North Sydney: NSW Health.
6. Kessler, R.C., Berglund, P., Delmer, O., Jin, R., Merikangas, K.R., & Walters, E.E. (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry, 62(6): 593-602.
7. National Comorbidity Survey. (2005). NCS-R appendix tables: Table 1. Lifetime prevalence of DSM-IV/WMH-CIDI disorders by sex and cohort. Table 2. Twelve-month prevalence of DSM-IV/WMH-CIDI disorders by sex and cohort. Accessed at: http://www.hcp.med.harvard.edu/ncs/publications.php
8. American Psychiatric Association. (2013) Diagnostic and statistical manual of mental disorders, (5th ed.). Washington, DC.
9. Pajević I, Sinanović O, Hasanović M. Association of Islamic Prayer with Psychological Stability in Bosnian War Veterans. J Relig Health. 2017 Dec;56(6):2317-2329. doi: 10.1007/s10943-017-0431-z.
10. Gallegos AM, Crean HF, Pigeon WR, Heffner KL. Meditationand yoga for posttraumatic stress disorder: A meta-analytic review of randomized controlled trials. Clin Psychol Rev. 2017 Dec; 58:115-124. doi: 10.1016/j.cpr.2017.10.004.

Artificial photosynthesis transforms CO₂ into liquefiable fuels

Yu and Jain. Plasmonic photosynthesis of C1–C3 hydrocarbons from carbon dioxide assisted by an ionic liquid. Nature Communications, May 2019.

Scientists have recently established a reliable “artificial photosynthesis” paradigm to produce fuels from water, carbon dioxide, and visible light. With the help of sunlight, chemical reactions between water and CO₂ are catalyzed in plants to generate and store solar energy in the form of glucose. This process is called photosynthesis. In the new study, the researchers developed an artificial process that uses the same mechanisms of natural photosynthesis to convert CO₂ and water into liquid fuel by using electron-rich gold nanoparticles as a catalyst. Gold nanoparticles function in the same role as chlorophyll in natural photosynthesis in the absorbing of light and transferring electrons and protons to catalyze the chemical reactions between CO₂ and water. They are known to be efficient at absorbing light and do not break down or degrade like other metals. The energy stored in the bonds of the hydrocarbon fuel can be freed by the conventional method of combustion or by new-generation, environmentally-friendly power fuel cells, thus producing electrical current. By converting CO₂ into more complex molecules like propane, green-energy technology is now one step closer to using excess CO₂ to store solar energy for use when the sun is not shining and in times of peak demand. While the development of this CO₂-to-liquid fuel may be exciting for proponents of green-energy technology, the artificial photosynthesis process is nowhere near as efficient as it is in plants. New methods should be developed to increase the efficiency of the catalysts and downstream chemical reactions at much higher scales.

Brain area that watches for walls identified

Henriksson et al. Rapid Invariant Encoding of Scene Layout in Human OPA. Neuron, May 2019.

Neuroscientists have identified the part of the human brain whose duty is to help us perceive the barriers which define the navigable space around us, such as walls or ceilings, so that so we can avoid bumping into things and navigate safely through our environment. By way of vision we have an almost instant sense of where we are in space. Although this process feels effortless, it requires the coordinated activity of multiple brain regions and neurons working together to give us this sense of our surroundings. This process has remained unknown. But thanks to a new study, we are a step closer to solving the puzzle. Using cutting-edge brain-imaging technologies, researchers examined the mental responses of volunteers as they were shown images of various three-dimensional scenes. The images depicted a typical room with three walls, a ceiling, and a floor, but then were abruptly changed by the removal of a wall or a ceiling. By doing this repeatedly, the team could pinpoint how the participant’s brain encoded every scene. In the brain scans of the volunteers, one brain area called the occipital place area (OPA) clearly stood out. OPA activity represented the geometry of the scenes and activity patterns, reflected the presence or absence of each component, such as a ceiling or a wall, and projected a detailed picture of the overall configuration. Interestingly, OPA seemed to ignore the surface appearance of the various components such as colors or textures in order to focus only on the geometric patterns. The OPA managed to perform all the necessary computations needed to get a sense of a room’s layout extremely fast – in just 100 milliseconds. In the future, the research team plans to incorporate virtual reality technology to create more realistic 3D environments for participants to experience, hopefully achieving much deeper insights into how our brains process and makes sense of the visual information.

Gut segments are organized by function

Esterházy D. et al. Compartmentalized gut lymph node drainage dictates adaptive immune responses. Nature, April 2019.

As food enters our intestine, it goes through a windy and lengthy journey. A new study provides new insights into how our intestines maximize nutrient uptake while protecting the body from potentially dangerous invading microbes. At first glance, the intestines appear to have a uniform tissue structure. But when scientists looked at them closer, they found that our food-processing canal seems to consist of multiple compartments that pace the immune system’s reactions to the food passing through. Scientists uncovered these functional intestine segments in mice when they examined the intestinal structures called gut draining lymph nodes, which orchestrate immune responses. The researchers found that nodes in different parts of the intestines had different cell composition, and they saw different immune responses between segments when they challenged the mice with a pathogen. They observed less aggressive defenses in the first segments where nutrients are absorbed, and more forceful responses at the end, where pathogens are eliminated. Researchers plan to exploit these immunological differences between the gut segments for treating gastrointestinal disorders. For example, by targeting immune-suppressing drugs to the specific gut segment where they’ll have the most effect, it might be possible to dampen their side-effects. The spectrum of immune responses along the intestines could also be used to make new and better oral vaccines. Thus far, scientists’ efforts to design oral vaccines have been hampered by the difficulty of generating a robust immune response; it is possible that the muted immune response at the beginning of the intestines might be part of the reason why oral vaccines tend to be less effective than injections. Thus, targeting the distant end of the intestine might be much more efficient way of inducing the immune response required.

Why is this surface area so large? What could the wisdom behind it be? Tiny endoplasmic canals play a role in inner cell transportation and distribution of matter. ER is the organized industry district in the cell. Most of the factories of molecules produced by chemical reactions are found here. ER is the production spot in the cells of proteins and hormones. Consequently, a broad surface area is very necessary and important.

Different degrees (pH) of acid are necessary for each reaction. However, because the acid necessary for one reaction can negatively affect the other reactions, thousands of opposite, intricate and different reactions take place. For this reason, membrane surface areas need to be wide. Sometimes hundreds of protein molecules are produced in just a second in a cell. The rapid and flawless lining up side-by-side of tens, hundreds or thousands of amino acids can only be achieved with a knowledge and power that surpasses these very small structures.

Wrapping the inside of the cell like a web and forming a buffer against mechanical effects, ER is responsible for establishing the flexibility and soundness of the cell. In muscle cells, ER takes the name Sarcoplasmic Reticulum (SR), which has a very important duty in the contraction of muscles. The size of the surface area of SR in the muscles of the structural frame is proportionate to the speed of muscle contraction. Consequently, there is more SR in muscle cells where there is rapid contraction. SR also serves as a calcium depot in muscle cells. Normally calcium is a deadly poison for the cell, and for this reason it is kept out of the cell. The concentration of calcium outside the cell is 10,000 times more than it is inside the cell. However, SR stores calcium in the cell in its own body. Thus, it both prevents the cell from being harmed and it provides the necessary calcium for contraction.

ER has the duty of eliminating the poison in the liver cells from the body by means of gall. For example, jaundice-causing bilirubin is a deadly poison for the brain especially in newborn babies. If jaundice is not treated, motor loss (paralysis) and intelligence loss can result from brain damage. Bilirubin and glucuronic acid combine by means of some enzymes on the surface of ER in the liver and are thrown into the gall bladder. In this way ER plays an important role in making foreign matter harmless and in reducing the side affects of medications to a minimum. Babies’ sensitivity to some medications during the first three months of life is due to ER’s not yet being developed enough to eliminate their harmful effects.

If it is taken into consideration that all of these mechanisms exist in human, animal and plant cells, it can be clearly seen that a broad and complex structure in such a small volume and its many functions can only have been placed there by the All-Powerful whose knowledge, wisdom, artistry, will and power permeate every moment and every spot.

Celaloglu is a freelance writer from Turkey with a degree in biology.

At the same time as these events are happening almost simultaneously, information from my eyes and my finger is being sent to the brain so that my finger will move in the way I expect it to. For example, if the path of my finger’s movement is somehow blocked, my brain can redirect it.

However, the event described above is not that simple. Starting from the neurons and continuing until we reach the muscles, every element that acts during this process displays extraordinarily complex alterations at both cellular and molecular levels.

Consider muscle cells, since they are moderately well understood. Upon arriving at the muscle cell, the electrical impulse causes the voltage-sensitive calcium channels in specific compartments within the cell to open and release calcium into the cell. You might remember from high school biology that muscle contraction is the result of two proteins (myosin and actin) sliding over each other. Normally, actins are masked by proteins known as tropomyosin. During the waiting period, therefore, the interaction between myosin and actin, which leads to contraction, cannot occur. This is why the muscle cell releases calcium, for when calcium is free in the cell, it binds to tropomyosin and enables it to move. As a result, actin is free to interact with myosin.1

After that, millions of molecules containing energy, known as ATP, bind to millions of myosin proteins, and the muscle contracts. When the contraction ends, the freed-up calcium is stored once again in specific compartments. When calcium is not present, tropomyosins again mask the actin proteins, and millions of muscle cells revert to their initial position, ready to respond to another contraction.

I realize that all of this is hard for the average reader to understand. However, the events that take place are even more complicated.

Expressions like “ATP binds to myosin” and “calcium is stored in compartments” are, in fact, simplified ways of explaining a highly complex event. Since there is a reason for everything, our cells should contain something that is performing these functions and carrying out such events. If we expand this problem to its limits, we will have to understand that each cell contains a large set of rapid and specific chemical reactions that occur constantly and yet do not interfere with one another. Based on current scientific knowledge, we can say that enzymes conduct almost all reactions in a cell, and that DNA has all the necessary information to produce enzymes. Enzymes are protein molecules that speed up and regulate all of the reactions that take place in a cell. If there were no enzymes, the reaction that a cell carries out in seconds could only be completed in thousands of years, and consequently, life as we know it would not exist. Life requires that the correct enzyme be found in the correct place and at the correct concentration.

Based on this, let’s revisit the above example. When the electric impulse reaches the muscle cell and calcium ions are released, this and every external and internal signal is conveyed to the DNA through a mechanism that we are just beginning to appreciate: signal transduction. Later, RNA is produced in those regions of the DNA that are responsible for producing the enzymes that enable the cell to give the appropriate answer (RNA helps DNA to produce enzymes). The synthesis of the enzyme is regulated at various checkpoints, such as during RNA production or RNA translocation out of the nucleus by other enzymes.2 ATPase, one of the many enzymes produced, makes it possible to use ATP, while another enzyme makes sure that the ATPases are in the correct location in the cell. Meanwhile, in order to sustain life, thousands of other enzymes conduct various reactions at the correct time and place. Therefore, when I move my finger, the number of active elements increases enormously.

Let’s look at the finer points of the cell. Using a simple calculation, in which each number is much smaller than the actual number used, if we assume that one million cells perform some kind of action from the reception of the first impulse in the brain until the time the muscle contracts, and if we calculate that one thousand reactions occur in each of these cells, this means that one billion reactions are performed for the simple action of moving a finger. One billion reactions, in just one second. And at the same time, my heart is beating, new blood cells are being produced, my eyes are sending visual information to my brain, my kidneys are filtering my blood, my lungs are exchanging old air with new, fresh air, my digestive system is supplying the necessary nutrients to my blood stream, and much, much more. Moreover, all of these are continually taking place. The fact that all of these actions are occurring, again based on a very rough and simple calculation, means that maybe one trillion reactions are occurring every second. As a result, a person might feel that it is quite possible, at any instant, for this perfect machine-the human body-to fall apart.

Realizing this, one might actually find it hard to believe that he or she is really alive. For example, I would never believe that such a machine would work if I did not have the empirical knowledge that it does work. How, for example, can I believe that I can produce one trillion reactions every moment and never confuse one with another, that it takes one billion reactions to move my finger, and that one trillion gears are working by themselves without making any mistakes?

With this idea in mind, I see the following lines in Epitomes of Light: “Also, since a building that contains every kind of artwork and riches cannot exist without having been built by someone, the existence of this universe is intimately connected with the existence of the Builder. If someone thinks carefully, it is impossible to accept one without the other.”3 Upon reading these words, I start to realize that all of these gears are not working by themselves, but rather that every second all of the trillion gears are being regulated by the One for whom nothing is difficult.

Suddenly, I remember that whenever the names of God are recited, I hear the name al-Hayy right next to al-Qayyum: God is He besides Whom there is no god; He is al-Hayy (the Ever-Living), al-Qayyum (the One Who sustains and protects all that exists) (Qur’an 2:255). Putting al-Qayyum next to “life” indicates, at least to me, that every living being is kept alive at each instant by al-Qayyum. If His control over each person’s existence were to be lost for even one second, one trillion gears would become irreversibly mixed up and the body would fall apart instantly. While thanking God for all that He has given me, I realize that I cannot thank Him enough for even one gear.

References

1. Harvey Lodish et al., Molecular Cell Biology, New York: Scientific American Books, c1995, 1027-29.
2. Lewin, Benjamin, Genes VI, Oxford, NY: Oxford University Press, 1997, 847.
3. Nursi, S., Epitomes of Light: Mathnawi al-Nuriya: The Essentials of the Risale-i Nur, Kaynak A.S., 1999.