We all focused on one topic throughout 2020: Covid-19. No single day passed without news on the pandemic as we counted numbers of positive cases and the death toll while anticipating for a vaccine. In the meantime, we got more familiar with some of the medical processes, like phases, clinical trials, mutations, etc. for all this had to deal with the most precious gift we are given: life.

In our last issue, we touched upon the history of pharmacology and how modern-day drugs are made in an article titled “Pharmacology: The Journey of a Chemical Compound into a Drug.” Now, we will explore the multiple, lengthy phases of clinical trials that drugs must undergo and why they are imperative in order for new medicines to get approved for the marketplace.

Clinical trials are a way to test new methods of diagnosing, treating, or preventing health conditions. The goal is to determine whether a substance is both safe and effective. A clinical trial is only done when there is strong reason to believe that a new test or treatment may improve the care of patients.

A variety of treatment methods such as medications, medication combinations, new uses for existing medications, and medical devices are evaluated through clinical trials. In the United States, all new treatments must go through these trials before being approved for public sale by the Food and Drug Administration (FDA).

At the discovery and development stages, thousands of compounds may be potential candidates for development into a “drug”. After early testing, however, only a small number of compounds look promising and call for further study. The entire process of developing a drug from its pre-clinical research stage to its final marketing phase can take approximately 12 to 18 years and often costs well over $1 billion [3, 4].

Clinical trials show us what works and what does not in the realm of healthcare and are designed to answer some important questions such as:

• Does the new treatment work in people? If it does, how effective is it?
• Is it better than currently used treatments?
• If it is not better, is it just as good and cause fewer side effects?
• Does it work in some people who do not benefit from current treatments?
• Is the new treatment relatively safe? There is virtually no treatment or procedure that is without risk, but do the benefits of the new treatment outweigh the risks?

Answering these questions, while giving as few people as possible an unknown treatment, often requires several clinical trials in different phases. Each phase is designed to answer certain questions while keeping trial participants as safe as possible.

Preclinical phase

Before clinical trials can begin in humans, tests and treatments are assessed in pre-clinical research, which can involve extensive laboratory research over several years of testing on animals and human cells. This research may aim to learn the chemical compound of a drug [1]. If the initial laboratory research is successful, researchers send the data to health authorities for approval in order to begin research and testing on humans.

Once pre-clinical research results are approved, human testing of experimental drugs can begin and is typically conducted in four phases that are denoted by Roman numerals (Phase I, II, III and IV). Each phase is considered a separate trial and, after completion of a phase over many years, researchers are required to submit their data to, and then wait for approval from their local health agency (the FDA in the US) before continuing onto the next phase. If the drug successfully passes through Phases I, II, and III then it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are “post-marketing” or “surveillance” studies that are conducted to monitor how safe the product is over several years [2].

Phase I

This is the first clinical phase that involves humans. Phase I trials most often include healthy volunteers, however there are some circumstances when clinical patients are used, such as patients who have terminal cancer or HIV. These treatments possess a much higher risk for healthy individuals and could cause to become ill and contract serious adverse side effects.

In a Phase I clinical trial, doctors collect information on:

• The dose or treatment
• When it should be taken, and how often
• Any side effects or complications
• How the treatment affects patients and their preexisting conditions

One of the primary goals of Phase I studies is to find the highest dose of a new treatment that can be given safely without causing severe side effects. Although the treatment has been tested in laboratory and most likely been used in animal studies, the side effects in people cannot be known for sure. During Phase I of a clinical trial, researchers spend several months to evaluate safety, side effects, optimal dosage amounts, and formulation method for the drug on about 20 to 80 people who have no underlying health conditions.

In addition to evaluating safety and ideal dosage, specialists also look at the best way to administer the drug such as orally, intravenously, or topically. These trials are often conducted in a clinical trial clinic where the subject can be observed by full-time staff. Safety always remains the foremost concern in Phase I. The research team keeps a close eye on the people and watches for any severe side effects.

Researchers start by giving very low doses of the drug to a few patients while higher doses are given to other patients until side effects become too severe or desired effects are seen. The drug may help patients, but Phase I trials are to test a drug’s safety. If a drug is found to be safe enough, it can be tested in a Phase II clinical trial. According to the FDA, approximately 70 percent of medications move on to Phase II.

Phase 2

Phase II of a clinical trial usually involves anywhere from 50 to several hundred who are living with the condition that the new medication is meant to treat. They are usually given the same dose that was found to be safe in the previous phase. Investigators monitor participants for several months, or years, to see how effective the medication is and to gather more information about any side effects it might cause.

Most phase II studies are randomized trials where one group of patients receives the experimental drug, while a second “control” group receives a standard treatment or placebo. These studies are mostly “blinded” which means that neither the patients nor the researchers know who has received the experimental drug in order to avoid from bias. Doctors use a computer program to randomly sort volunteers into these two separate groups. Each volunteer has an equal chance of ending up in any of the groups and are randomly put in any group.

This allows investigators to provide the pharmaceutical company and the health authority with comparative information about the relative safety and effectiveness of the new drug. When the development process for a new drug fails, this usually occurs during Phase II trials when the drug is discovered to not to work as planned or to have toxic effects. The FDA estimates that roughly one-third of experimental drugs successfully complete both Phase I and Phase II studies.

Phase II clinical programs historically have experienced the lowest success rate of the four development phases. In 2010, the percentage of Phase II trials that proceeded to Phase III was 18% [5] and only 31% of developmental candidates advanced from Phase II to Phase III in a large study of clinical trials conducted during the period of 2006 – 2015 [6].

Phase III

Phase III of a clinical trial usually involves up to 3,000 participants who have the condition that the new medication is meant to treat. These participants must include men, women, and people of different ages and ethnic groups in many places across the country (or even around the world) at the same time. This helps doctors learn how treatment works in different people with different genetic backgrounds, races, and ethnicity. These studies tend to last longer – up to several years – than Phase I and II studies.

One of the additional purposes of Phase III is to evaluate how the new medication works in comparison to existing medications for the same condition. To move forward with the trial, investigators need to demonstrate that the medication is at least as safe and effective as existing treatment options. Due to the larger number of participants and longer duration of Phase III, rare and long-term side effects are more likely to show up during this phase.

There can be more than two treatment groups in Phase III trials. The control group may receive the current standard-of-care treatment for their illness while other groups receive the new treatment on trial. Phase III trials are usually double blinded to eliminate bias when interpreting results.

Placebos may be used in some Phase III studies, but they are never used alone if there is a treatment available that works. Sometimes, a patient who is randomly assigned to the placebo for part of the study will at some point be offered the standard treatment as well. As with other trials, patients in Phase III clinical trials are watched closely for side effects, and treatment is stopped if they become too hard to manage.

Every patient in a Phase III study is watched closely, and the study will be stopped early if the side effects of the new drug are too severe or if one group has significantly better results. Phase III clinical trials are often needed before the FDA will approve the use of a new drug for the general public. If researchers demonstrate that the medication is at least as safe and effective as others already on the market, then the FDA will usually approve the medication.

In the United States, when Phase III clinical trials (or sometimes Phase II trials) show a new drug is more effective or safer than the current treatment, a new drug application (NDA) is submitted to the FDA for approval. The FDA reviews the results from the clinical trials and other relevant information.

Based upon the review, the FDA then decides whether to approve the treatment for use in patients with the illness the drug was tested on. If approved, the new treatment often becomes a standard of care and newer drugs may be tested against it before they can be approved. If the FDA feels that more evidence is needed to show that the new treatment’s benefits outweigh its risks, it may ask for more information or even require that more studies be done. Once Phase III is complete, a pharmaceutical company can request FDA approval to begin marketing the drug. Roughly 25 to 30 percent of medications move on to Phase IV.

Phase IV

Phase IV trials test new drugs that are approved by health authorities and often are called Post Marketing Surveillance Trials. The drugs are available for doctors to prescribe to patients, but Phase IV studies might still be needed to answer important questions. In previous clinical phases the drug may not have been tested for interactions with other drugs, or on certain population groups, such as pregnant women, who are unlikely to subject themselves to trials. This phase involves thousands of participants and can last for many years. Investigators use this phase to get more information about the medication’s long-term safety, effectiveness, and any other benefits.

This is often the safest type of clinical trial because the treatment has already been studied a lot and has likely been given to many people. Phase IV studies look at safety over time. These studies may also look at other aspects of the treatment, such as quality of life or cost effectiveness.

Phase IV studies can result in a drug or device being taken off the market or restricted depending on the findings in the study. Unless an adverse effect of the approved drug is shown or the drug is accepted as safe, it will stay on the market and also in Phase IV forever.

This clinical trial algorithm has come out after many scientific studies. Every point of the clinical trials, and possible problems, have been clarified by policies which may differ from country to country. At the end, clinical trials are a very safe and cautious method of finding out the safest and most effective treatment, or diagnostic method, for people. During clinical trials, scientists are very careful about ethical issues and try not to harm any living organisms, be them animals or humans. There is an ongoing public debate over pharmaceutical companies. While some think they play a major role in the emergence of many methods and scientific developments to benefit human health, others doubt their motivations and questions their contribution to the public good. This debate will surely continue for a long time, but under the current circumstances, pharmaceutical companies are found in the center of all these clinical trials described in this article. Regardless of the truth behind these doubts, it is important to be always aware of the priceless value of life, that it has been given to us and all living things as an inalienable right and a precious gift, and that it is a major responsibility take care of it well and seek healing when needed.

• https://www.nccn.org/patients/resources/clinical_trials/phases.aspx
• “The drug development process”. US Food and Drug Administration. 4 January 2018. Retrieved 17 August 2020
• Holland J (2013). “Fixing a broken drug development process”. Journal of Commercial Biotechnology. 19. doi:10.5912/jcb588.
• Adams CP, Brantner VV (2006). “Estimating the cost of new drug development: is it really 802 million dollars?”. Health Affairs. 25 (2): 420–8. doi:10.1377/hlthaff.25.2.420. PMID 16522582.
• “New drugs failing Phase II and III clinical trials”. MedCity News. 2011-06-02.
• “Clinical Development Success Rates 2006-2015” (PDF). bio.org. Retrieved 2018-02-11.

To this day, natural breast milk is still regarded as the best nutritional choice for babies. Recent research on stem cells, genetics, and epigenetics [1] from the last three decades, along with information obtained from studies about childhood and youth and testimonials from organizations that guide health policies worldwide, all support this claim. Modern medicine agrees that breastfeeding is the healthiest, most inexpensive, highest quality, and most appropriate choice for protecting both a mother and baby’s health [2]. The World Health Organization holds breastfeeding as an essential gold standard for the immunological development of a child, starting from the first six months to two years of age [3].

Breastfeeding has many benefits. It strengthens the emotional bond between the mother and her baby. It helps ensure that the baby grows in a healthy manner, by establishing its first feeling of trust; positively effects the baby’s intelligence level; and helps bolster the baby’s immune system.

One of the most studied issues in recent studies is the effect of breast milk on respiratory diseases such as asthma. The effects of breastfeeding on asthma, allergic diseases, and respiratory infections has been a topic of concern for the medical world for at least the last 80 years. Recent studies agree that breast milk has a preventive role against lower respiratory tract infections in infancy (0–2 years). However, there are some complications in these studies. Given the challenges in patient standardization, only food-allergy studies can be standardized. Due to the complexity of the environmental and genetic factors that trigger allergies, it should be considered normal that the effect of breast milk has not yet been fully established to protect against a wide range of allergic diseases, particularly asthma [4].

Asthma is the most common chronic disease in childhood and has a complex structure. It has been on the rise lately, and scientists are scrambling to figure out what is causing this increase as well as the best ways to combat the disease. Asthma can be caused by a wide variety of sources, such as genetics, smoking, microscopic ticks and mites in house dust, allergenics such as grass or pollen, obesity, urban life, air pollution, synthetic nutrition, and imbalance in intestinal flora [5]. In addition, premature birth, low birth weight, a young mother, and early exposure to respiratory infections are factors that increase the risk of asthma [6]. Consequently, it is difficult to independently measure the effect of a single determinant in asthma. In a significant study on 3,963 children in the Netherlands, children were breastfed for at least four months and then followed for up to eight years after birth. The outcomes of the study revealed that breast milk significantly reduced the risk of asthma, independent of other variables. It has been observed that the rate of chronic asthma development decreases as the breastfeeding duration increases [7].

Today, breast milk’s benefits have been proven in protecting babies from respiratory infections both early on and later in life. Breastfeeding provides an emergency line of defense against infectious diseases by helping infants whose immune systems are not yet developed enough to fight infections.

Breastfeeding facilitates a beneficial germ exchange between mothers and babies and helps to develop a strong immune system. Enzymes, hormones, bioactive molecules, and growth factors in breast milk are all extremely vital for babies. These crucial molecules help develop the baby’s immune system by interacting with the proximate elements. Thanks to numerous features in its ingredients, breast milk has a significant role in supporting the baby’s immune system with the development of appropriate microorganisms in the intestine. The strength of the microbial structure in the baby’s intestine depends on the way of delivery, diet, and the variety of foods consumed by the mother. This healthy structure in the intestines is essential for the development of the immune system and for building an increased tolerance to new foods that will be taken orally. In infancy, beneficial microbiota in the intestines starts to develop healthily by breastfeeding in the first four to six months.

A comparative study between the intestinal flora of infants fed with breast milk and formula milk showed that the diversity and density of the desired microorganisms increased in a shorter time and in sufficient amount in the breastfed infants. Today, increased hygiene standards have changed the intestinal flora of infants, especially in Western societies. This, however, has increased the risk of diseases such as asthma [8].

Cytokines (a group of proteins and peptides that allow cells to communicate with each other) in breast milk also serve the development and smooth functioning of the immune system and play an important role in protecting the baby against bacterial infections, wheezing, and allergies. Human milk, especially “first milk,” was found to contain more than 20 cytokines [9]. First milk arrives in the first few hours after birth as a miraculous gift to babies when they are most vulnerable to illnesses and helps to protect against diseases. Ig A antibodies in the first milk also protect against infectious diseases that are commonly experienced in early life, besides obesity, diabetes, and allergic diseases that may come later [10].

Infants fed with ready-made foods have lower amounts and types of bacteria in their intestines than those fed with breast milk, which can consequently increase the risk of eczema and asthma. The issue of delaying foods with high allergy potential, especially when switching to supplementary foods, is still being debated. Some researchers suggest that complementary foods should not be introduced to infants up to 12 months. However, the common opinion is that positive intestinal bacteria that develops with sustained breastfeeding can reduce the risk of allergies to additional foods. Another consensus is that the transition to supplementary foods should not be earlier than six months [11].

As breast milk is the most important food for newborns, mothers should diligently endeavor to complete the suggested period of breastfeeding. Breastfeeding, if continued until the age of two and especially in the first six months, is accepted by international pediatric authorities as the cornerstone of nutrition.

Character formation and breast milk

We are physically and emotionally affected by what we eat or drink. Based on this assumption, it can be argued that breastfeeding might also have an influence on the character formation of babies [12]. Although it has been determined that intelligence and brain development are influenced by the emergence or inhibition of some genetic characters in the baby by epigenetic means, no research based on long-term observations has been conducted. In any case, it would be wise for parents to provide the best food both for themselves and their babies. Inasmuch as they make sure the food is hygienic and natural, they should also be cautious that it is obtained through legitimate means. If, for any reason, the mother’s milk is not enough or is suspended, a milk-mother with necessary qualities may be contracted.

Breastfeeding for two years is prescribed in the Qur’an: “Mothers are to suckle their children for two complete years” (2:233). “We have enjoined on human in respect with his parents: his mother bore him in strain upon strain, and his weaning was in two years” (31:14). Likewise, the Prophet Muhammad, peace be upon him, speaking about his son Ibrahim, who died before he could turn two, said, “He has a milk-mother in Paradise, she will suckle him for his remaining milk, (will complete the term of two years).” (Muslim, Fadail, 63, 2316)

References

1. The inherited and non-genetic changes which occur in the disclosure of genetic information i.e. gene expression, without any no change to the structure of DNA.
2. Ballard O, Morrow AL: Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am, 2013; 60: 49–74.
3. World Health Organization Recommendations on Postnatal Care of the Mother and Newborn. Geneva, WHO, 2013.
4. Matheson M, Allen KJ, Tang MLK: Understanding the evidence for and against the role of breastfeeding in allergy prevention. Clin Exp Allergy, 2012; 42: 827–851.
5. Ding G, Ji R, Bao Y: Risk and protective factors for the development of childhood asthma. Paediatr Resp Rev, 2015; 16: 133–139.
6. Oddy WH, de Klerk NH, Sly PD, Holt PG: The effects of respiratory infections, atopy and breastfeeding on childhood asthma. Eur Respir J, 2002; 19: 899–905.
7. Scholtens S, Wijga AH, Brunekreef B, Kerkhof M, Hoekstra MO, Gerritsen J et al..: Breastfeeding, parental allergy and asthma in children followed for eight years: the PIAMA
8. birth cohort study. Thorax 2009; 64: 604–609.
9. Adlerberth I, Wold AE: Establishment of the gut microbiota in Western infants. Acta Paediatr, 2009; 98: 229–238.
10. Goldman AS, Rudloff HE: Are cytokines in human milk? Adv Exp Med Biol, 1991; 310: 93–97.
11. World Health Organization Recommendations on Postnatal Care of the Mother and Newborn. Geneva, WHO, 2013.
12. World Health Organization: Global Strategy for Infant and Young Child Feeding. Geneva, 2003.
13. Ibrahim Canan, Peygamber’in Sunnetinde Terbiye, Istanbul: Isik Yayinlari, 2014, pp. 95.

Being a native Indian tree, the Moringa also grows in tropical countries, such as Nigeria. Although its leaves have long been eaten or brewed for health benefits, its effectiveness has not yet been recognized in other parts of the world. Often called the “miracle plant,” there has been a significant amount of research done on the therapeutic properties of the moringa, and this research will hopefully spread knowledge of its healing qualities.

The literature mentions its antioxidant, anticancer, anti-inflammatory, antidiabetic, and antimicrobial properties. Its leaves contain high-quality protein, and the seeds have lipid (fat) in abundance [1]. That is why moringa has a great deal of calcium, potassium, sodium, and iron [2]. It is claimed that moringa has twelve times more vitamin C than oranges, ten times more vitamin A than carrots, seventeen times more calcium than milk, nine times more protein than yogurt, and twenty-five times more iron than spinach.

Moringa is used to treat more than 300 illnesses, especially in Africa. The ancient Egyptians used it as skin cream. Since then, more and more of its cosmetic benefits have been discovered, and it has found a unique place among health-care products today [3]. Moringa is used to accelerate hair growth; treat illnesses such as excessive hair oil, dandruff, and inflammation of the scalp; treat skin wrinkles, blackheads, and pimples in the skin; and to manage eczema and psoriasis. To determine the plant’s ultimate effectiveness, more research and lab work are needed.

After oil extraction, moringa’s seeds and leftovers are used as an organic fertilizer which increases farming efficiency [4]. The seeds, leaves, oil, sap, shells, roots, and flowers are also used for cooking and treatment. The leaves of the plant can be brewed as tea and can be eaten raw as a vegetable.

More than 400 studies carried out over many years have looked into moringa’s effects on illnesses [5]. The significant findings can be summarized as follows: it has been shown to strongly reduce [6] cholesterol and blood fat as well as the atherosclerotic plaques; this effect can even be achieved with the oral consumption of the plant. When peeled, the moringa fruit’s shell reveals a soft white seed, like a chickpea-sized cotton. The seed can be consumed by swallowing it. The moringa’s roots and branches can be grounded and used as powder.

The studies have also revealed that moringa’s usage can help with improving numerous conditions, including but not limited to liver infections such as hepatitis [7], lowering the glucose levels in blood in patients with Diabetes Type-2 [8], various gastrointestinal problems, increasing milk production in nursing mothers, regulating kidney functions, Parkinson’s disease [9], and atopic dermatitis [10].

Some of the studies carried out examine how safe moringa is. People have a general inclination towards consuming natural plants without paying attention to how much they intake. Unfortunately, there are many life threatening and poisonous plants – and other plants that can be dangerous when taken in large quantities. Trying to identify the safety range of moringa, a study that lasted for 14 days examined the effects of it on mice that had depression and used anti-depressants. Researchers found out that moringa does not cause toxicity, provided that the dose does not exceed 2 grams per 2.2 pounds of weight [11]. It would be wise to utilize this plant after the testing process has been completed on humans, and a guide is prepared to show the types of illnesses and the corresponding doses.

Illness is a fact of life. Thankfully, the universe has been created with plants like moringa, which can be used to ease our pains and illnesses. We owe it to ourselves, and to other humans, to study all facets of the universe, including the moringa plant.

References

1. Stohs SJ, Hartman MJ. Review of the Safety and Efficacy of Moringa oleifera. Phytother Res. 2015 Jun;29(6):796-804.
2. Raimunda S, Nogueira B, Jamille AS et al. Research advances on the multiple uses of Moringa oleifera: A sustainable alternative for socially neglected population. Asian Pac J Trop Med 2017;10:621-30.
3. Fahey J. Moringa oleifera: a review of the medical evidence for its nutritional, therapeutic, and prophylactic properties. Trees Life J 2005;1:1-33.
4. Emmanuel SA, Emmanuel BS, Zaku, SG, Thomas SA. Biodiversity and agricultural productivity enhancement in Nigeria: Application of processed Moringa oleifera seeds for improved organic farming. Biol J N Am 2011;2:867-71.
5. Matic I1, Guidi A2, Kenzo M3, Mattei M2, Galgani A2, Investigation of medicinal plants traditionally used as dietary supplements: A review on Moringa oleifera. J Public Health Afr. 2018 Dec 21;9(3):841. doi: 10.4081/jphia.2018.841. eCollection 2018 Dec 21.
6. Chumark P, Khunawat P, Sanvarinda Y, et al. The in vitro and ex vivo antioxidant properties, hypolipidaemic and antiatherosclerotic activities of water extract of Moringa oleifera Lam. leaves. J Ethnopharmacol 2008;116:439-46.
7. Almatrafi MM, Vergara-Jimenez M, Murillo AG, et al. Moringa Leaves Prevent Hepatic Lipid Accumulation and Inflammation in Guinea Pigs by Reducing the Expression of Genes Involved in Lipid Metabolism. Int J Mol Sci 2017;18:E1330.
8. Kumari DJ. Hypoglycaemic effect of Moringa oleifera and Azadirachta indica in type 2 diabees mellitus. Bioscan 2010;5:211-4.
9. Giacoppo S, Rajan TS, De Nicola GR, et al. The Isothiocyanate Isolated from Moringa oleifera Shows Potent Anti- Inflammatory Activity in the Treatment of Murine Subacute Parkinson’s Disease. Rejuvenation Res 2017;20:50-63.
10. Choi EJ, Debnath T, Tang Y, et al. Topical application of Moringa oleifera leaf extract ameliorates experimentally induced atopic dermatitis by the regulation of Th1/Th2/Th17 balance. Biomed Pharmacother 2016;84:870- 7.
11. Kaur G1, Invally M1, Sanzagiri R1, Buttar HS2. Evaluation of the antidepressant activity of Moringa oleifera alone and in combination with fluoxetine. J Ayurveda Integr Med. 2015 Oct-Dec;6(4):273-9. doi: 10.4103/0975-9476.172384.

It is widely accepted in modern culture that people should eat three meals: breakfast, lunch, and dinner. Nutritionists generally recommend adding two snacks (one in the morning and the other in the afternoon) to help control appetite.

Interestingly, the practice of eating three meals a day is a recent phenomenon. Ancient Romans had only one meal, which they usually had at about four in the afternoon, and they believed it was unhealthy to eat more than once a day. What the Romans ate in the morning and at noon was very light and fast [1]. Later, rules in monasteries affected people’s behavior around food and drink.

During the industrial revolution, breakfast gained importance; workers needed food before work. And dinner didn’t become popular – at least in its current form – until the prevalence of artificial lighting made it possible to eat before dawn and after dusk [2]. The understanding that eating three meals a day is a healthy choice stems from a combination of belief, culture, and early epidemiological studies [3].

There are studies suggesting that having a regular eating habit positively impacts health, regardless of frequency of meals. On the other hand, in a recent and comprehensive study by Kahleova et al., which studied 50,660 adult members of churches in the USA and Canada, it was found that eating one or two meals a day caused lower weight than eating three meals, and also a relatively lower body-mass index (BMI) which got even lower as overnight fasts got longer [4]. The authors state that the positive effects of such a diet are caused by a combination of timing, meal frequency, and overnight fasting, as well as having less frequent meals coupled with precise timing. These results indicate that eating one or two meals is better than eating three or more.

The Prophet’s example

The Prophet Muhammad’s, peace be upon him, recommendations and behaviors lend support to modern medical studies in the area of nutrition, as in many others. He would eat no more than two meals and ensure that one of the meals should consist of light food (such as dates). The Prophet recommended that dinner be eaten, even if it was only a small meal. “Do not leave dinner, even if it is only a handful of dates, because abandoning it makes one weak” (Sunan Ibn Majah).

He defined dinner as the second and last meal of the day, and that it should be eaten after dusk or immediately after the evening prayer.

The Prophet set so many examples about nutrition. He highlighted the dangers of obesity, stating that “What I fear most about my community are developing a belly, oversleeping and idling.” This was centuries ago; nowadays, obesity is an epidemic raging across the world, and its prevalence has almost doubled in more than 70 countries since 1980. In 2015, a total of 107.7 million children and 603.7 million adults were obese [5]. Seventy-five percent of the world’s population is overweight. Obesity, along with dyslipidemia and hypertension, is one of the major factors in cardiovascular diseases. Studies have shown that exercise, as well as meal timing and frequency, are quite effective in weight control [6].

As for table manners, the Prophet said, “The human does not fill any container that is worse than his stomach,” and, “It is sufficient for the son of Adam to eat what will support his back.” Throughout his 63-year-long life, the Prophet never left the table on a full stomach or ate before getting hungry; he recommended that food should not be swallowed without chewing, a practice he maintained. By refusing to sit at tables where there were several types of food, our Prophet was occasionally unable to find anything to eat. There is also no information that our Prophet ever had lunch.

The Prophet’s insistence on fewer meals looks very wise. Not only does eating fewer meals lead to lower incidences of obesity; if it includes a reduction in carbohydrate intake, it can also lead to decreases in total and LDL (bad) cholesterol levels [7]. Considering meal frequency and timing, it is crucial which meals are maintained. In general, breakfast-eaters tend to run a lower risk of weight gain than non-breakfast-eaters – and a significantly lower risk of heart disease [4].

Current studies indicate that food content has as much impact on blood lipids and insulin as meal frequency. Although we cannot fully explain the effects of a single factor on physical health, we are pretty much sure that meal frequencies are closely related to meal timing and which kind of foods are eaten.

The Prophet’s main requirement of food was that it should be lawful and clean, as well as beneficial for the body. His two meals consisted of breakfast and dinner, as is recommended by modern medicine. In a nutshell, the amount of intake and eating etiquette recommended by our Prophet is allocating “one third of the stomach for food, one-third for drink, and one-third for air” (Tirmidhi, Zuhd, 47) and completing meals without getting full. Increasingly, science suggests this may have been good advice!

References

1. Flandrin, J.-L.; Montanari, M. Storia dell’alimentazione; Laterza: Bari, Italy, 2003. 2.Affinita, A.; Catalani, L.; Cecchetto, G.; De Lorenzo, G.; Dilillo, D.; Donegani, G.; Fransos, L.; Lucidi, F.; Mameli, C.; Manna, E.; et al. Breakfast: A multidisciplinary approach. Ital. J. Pediatr. 2013, 39, 44.
2. Potter, C.; Griggs, R.L.; Brunstrom, J.M.; Rogers, P.J. Breaking the fast: Meal patterns and beliefs about healthy eating style are associated with adherence to intermittent fasting diets. Appetite 2018, 133, 32–39.
3. Kahleova, H.; Lloren, J.I.; Mashchak, A.; Hill, M.; Fraser, G.E. Meal frequency and timing are associated with changes in body mass index in adventist health study 2. J. Nutr. 2017, 147, 1722–1728
4. Collaborators, G.B.D.O.; Afshin, A.; Forouzanfar, M.H.; Reitsma, M.B.; Sur, P.; Estep, K.; Lee, A.; Marczak, L.; Mokdad, A.H.; Moradi-Lakeh, M.; et al. Health effects of overweight and obesity in 195 countries over 25 years. N. Engl. J. Med. 2017, 377, 13–27.
5. Paoli, A.; Moro, T.; Marcolin, G.; Neri, M.; Bianco, A.; Palma, A.; Grimaldi, K. High-intensity interval resistance training (hirt) influences resting energy expenditure and respiratory ratio in non-dieting individuals. J. Transl. Med. 2012, 10, 237.
6. McGrath, S.A.; Gibney, M.J. The effects of altered frequency of eating on plasma lipids in free-living healthy males on normal self-selected diets. Eur. J. Clin. Nutr. 1994, 48, 402–407.

It is estimated that there are approximately 100 trillion cells in the human body. They fulfill their duties harmoniously with all the systems, organs, and tissues manifesting innumerable signs of wonder and wisdom. If a disruption occurs to the working of cells or the coordination among cells, the process leading to cancer starts to develop in the body’s tissue.

The recent increase in cancer occurrences has led researchers to look into its development. The phrase “cellular anarchy” is sometimes used to refer to cancer’s development. Indeed, when we examine the mechanism of cancer development, we see that cells engage in irregular – anarchic – activities in addition to regular ones.

Abnormalities emerge in cancerous cells during cell division and differentiation (when they transform into specialized cells according to different tissues). Cancer cells divide uncontrollably. Under normal circumstances, numerous genes are active in cell division. In cancerous cells, however, failures occur in the mechanisms that control division. Moreover, due to differentiation flaws in cancerous cells, undifferentiated cells, which fail to acquire features that enable them to function in a tissue or organ, form groups of cells that constrain and damage other cells because of the space they occupy.

Checkpoints in cell division and tumor suppressing genes

How is cell division controlled in a normal cell?

Our cells go through numerous stages as they divide. The beginning of each stage is called a “checkpoint” because it is where errors in cell divisions are checked. At each checkpoint (called G1, S and G2) are proteins with certain duties. One of these proteins, P53, suppresses development of cancer. In other words, P53’s job is to prevent failures during cell division, hence blocking the path to cancer’s development in the cell. Whether there is a flaw in the DNA it is checked over and over again at each checkpoint. If no error is identified, the next stage proceeds. In this way, it is ensured that there is not any genetic error in the cells formed as a result of division. If there is an error, cell division is stopped. First an attempt is made to correct this genetic error. If it can be corrected, cell division is resumed. If the error is too big to be corrected, then the cell is scheduled to die; this is called apoptosis. It is worth remembering at this point that proteins that are too minute to be observed even by microscopes are tasked to perform these stupendous mechanisms. It is remarkable that they were designed to work so effectively.

Because these systems are disrupted during the development of cancer, genetically flawed cells form and multiply. Proteins produced with the genetic codes of the flawed cells are also flawed, and these flawed proteins cause a failure of the mechanisms that constrain cell division. Unconstrained cells have an abnormal capacity for division and they divide continuously, which is why cancerous cells have a greater ability to divide than normal cells.

Proto-oncogenes and oncogenes

It is essential that the parts of our body that grow, develop, or get damaged be repaired. In such cases, our cells synthesize certain “signal” molecules which are responsible for carrying to the nucleus the information that our cells should divide. As a result of the incoming information, some DNA regions called proto-oncogenes are stimulated and cell division gets underway. Proto-oncogenes are genes responsible for checking the start of cell division. When the human body encounters various cancer-making elements, damages occur in proto-oncogenes, which transform into oncogenes, or genes with the potential to cause cancer. Oncogenes lead a cell to develop cancer because cell division does not stop where it should and continues endlessly in the absence of healthy proto-oncogenes. Underlying abnormal tissue growth and spread to other organs is the fact that the control over cell division is lost.

Genetic treatment of cancer

It became apparent that age-old treatment methods proved wrong once it was discovered that the biological foundations of cancer stemmed from genetic disruptions. Despite its increase in the last century, cancer has in fact been seen throughout the history of mankind; even ancient Egyptian papyri talked about it. Because there was not a definite treatment for cancer, radical treatments were used, such as burning or cauterizing the tumor. In the first half of the twentieth century, only surgical methods were implemented in cancer treatments. Desired results could not be obtained by surgical procedures, which ended up with the excision of entire organs.

Research studies were launched in the second half of the twentieth century into whether it was possible to treat cancer using drugs. These studies revealed that cancer stemmed from genetic flaws (like the ones in oncogenes and tumor suppressing genes), which led to questions about types of treatment. Treatments of flaws at the genetic level are based on genes themselves. These treatments use such methods as stopping genes that work abnormally, eliminating the products of these genes, and killing cancer cells by making use of their genetic mechanisms.

New incidents of cancer are likely to continue to develop, for people are exposed to factors that cause disruptions of the makeup of genes. To prevent cancer, it is critically important that one should have a conscious, natural, and balanced lifestyle. People should be well-informed about the effects of smoking, genetically modified food, radiation, stress, and chemicals, so that they can lessen exposure to such risk factors. Moreover, more frequent implementation of screening tests will make early diagnosis easier. More effective methods with fewer adverse effects should also be developed for higher success rates in cancer treatment. Genetic treatment of cancer is a relatively new field but an increasing number of studies focus on it. These studies aim to kill only cancerous cells and spare healthy ones. It can be expected that research into this field will produce promising outcomes in coming years.

Embryonic stem cells are cells in the early stages of embryonic development when a fertilized egg cell is divided first into two cells and then into four, eight, and sixteen. Each grows into a brand new cell type and multiplies as per the codes present in its DNA program as tissues form and organization starts. 

After twenty years of research and accompanying debates on the human embryo, we are finally on the threshold of both reshaping our present concepts in biology and moving on to clinical case studies. The first human embryonic stem cells were produced in 1998. Studies researching the question, “Can we treat diabetes by reprogramming the DNA in these cells at the beginning of life?” switched first to how human genes worked and which genes are responsible for the development of particular tissues and then to the embryonic stem cells for these areas and ultimately to replacing or reprogramming a “faulty or deficient” gene.

The most controversial topics in genetics and embryonic studies are related to bioethics. Many scientists are grappling with questions like whether is it ethically correct to intervene with the genetic programming of a fertilized human egg (zygote)? If so, what should be the limits? Are we trespassing a divine domain?

Embryonic stem cells have been an excellent source of information that we lacked throughout history about how living organisms started to develop. Like astronomers who trace their knowledge to the Big Bang in order to obtain fundamental information about the origin of the universe, biologists have been researching how the molecules in a single cell went through sequential and planned changes, how they transformed and acquired new functions that triggered the mind-blowing developments in diverse, miraculous living organisms. Scientists have found out how primordial embryonic cells transformed into more than 200 cell types that constitute various tissues and organs. The number of studies has skyrocketed about which molecule types can be used to regenerate the damaged tissue, say, after a traffic accident. Embryonic studies that focus on the regeneration or reparation of medulla cells (spinal cord) have been a source of hope for some patients with permanent paralysis because of a broken back injury or severed spine in a traffic accident or those who are still stranded in wheelchairs. Similarly, the preliminary findings of research into Parkinson’s and diabetes are extremely promising, and a new study reports of two blind people with macular degeneration (which causes blindness) who have been treated.

Initial studies

In 1981 researchers successfully obtained stem cells from a rat embryo culture. They soon realized that the cells held a secret potential: they could grow into 200 different types of cells. Later Wisconsin-Madison University biologist James Thomson derived stem cells from primates for the first time. Three years afterwards, Thomson derived the first human embryonic stem cells from donated but unused embryos.

The increasing number of research studies into embryonic stem cells sparked off intense debate both in religious circles and among the science community that care passionately about the sanctity of humans. Allegedly, lab studies were conducted on human embryos without restrictions, which were grown until tissues and organs formed but were then killed. In 2001, the US president George W. Bush slashed federal funds, stating that stem cell research was not strictly ethical. Deriving embryonic cells was banned in many countries including Germany and Italy. In other countries, however, studies went full speed ahead. Indeed, reports flooded in about stem cells grown by researchers in Australia, Singapore, Israel, Canada and the USA into nerve cells, immune system cells, and heart cells.

Before long, a new idea emerged about transferring new cells into the egg cell – like nuclei of body cells used in cloning Dolly the sheep – to produce various tailor-made, fully DNA-compatible tissues and organs, as they had the same genome as the donor’s. It became a topic of everyday conversations that spare organs could be cultivated for the human body just like spare parts of cars or other machinery were produced to replace a faulty or damaged part. In fact, if it were not for claims such as “creating a new human” there would be no objections against producing a kidney, lung, or heart from the DNA of a patient and thus overcome the major problem of tissue rejection in transplantation of organs.

If faulty or defective genes could be removed and replaced by healthy genes in the DNA of stem cells, many incurable genetic diseases could easily be fixed and many prospective parents who avoid having a child because of a defective gene they carry would welcome the development enthusiastically.

We are on the threshold of reshaping our present concepts in biology and moving on to clinical case studies. Embryonic studies have been a source of hope for even patients with diseases like paralysis and blindness.

Just in time and in the right amount

Embryonic stem cells are cells in the early stages of embryonic development when a fertilized egg cell is divided first into two cells and then into four, eight, and sixteen. Each grows into a brand new cell type and multiplies as per the codes present in its DNA program as tissues form and organization starts. It is most mysterious and miraculous that the molecules that lead a stem cell to transform into a new type of cell are synthesized at exactly the right moment and in the precise amount.  Scientists are currently trying to figure out which molecule leads a cell to become a nerve, muscle, or bone cell when attached to it. They are likely to decode the molecules by monitoring the tissues that remain undeveloped because of missing genes resulting from DNA mutations observed in certain genetic diseases.

The new field that has developed in the last two decades called regenerative medicine is predicated on tapping into the potential of stem cells by repairing missing or faulty tissues, or completing a link in the chain necessary for the functioning of a dysfunctional metabolic process. In 2006, stem cell biologist Shinya Yamanaka of Kyoto University in Japan successfully transformed adult rat cells into an embryonic state. The following year, human body cells were transformed into embryonic stem cells. The ensuing research has led to the acknowledgement that it was theoretically possible to transform stem cells into any cell type, a promising cure for diseased embryos that have genetically missing parts.

The major problem, however, is keeping these delicate cells alive in a culture medium. In 2007, Yoshiki Sasai discovered a molecule called rock inhibitor that nourished the cell colonies he grew. The success rate in generating new cell colonies rose to 27%. Parmar from Swedish Lund University heralded “a new golden era” by producing new neurons from embryonic stem cells for the treatment of Parkinson’s.

As new techniques were developed for producing cells fast and reliably, these cells turned out to involve a very low risk of developing cancer. “We don’t yet know how this hidden power and balance that can be transformed into any cell type is controlled,” states Hiromitsu Nakauchi, a stem cell biologist at Tokyo University who researches making blood platelets out of stem cells derived from the embryo or somatic cells.

Experiments are underway that aim to treat disorders by activating stem cells stored in the body that have not yet differentiated through the help of proper stimulating molecules. 

Miraculous differentiation

As the techniques for producing and feeding stem cells got easier, researchers aimed at growing and forming tissues and organs. A connective tissue or an outer covering like the skin that lacks a shape but takes the shape of the underlying muscles and bones can be produced even in a Petri dish and then transplanted to a burned or missing area of the skin. The present aim is the production of organs such as the kidney or the heart that has a particular shape and is made up of a number of different tissues. If the correct signal molecules responsible for cell division and differentiation can be identified and readily used where necessary and at the right amount, then organs including any type of tissue can be produced. Researchers like James Wells at Cincinnati Children’s Hospital in Ohio have tested the damage of drugs on intestines by using the partial intestines they developed from stem cells rather than administer them to normal humans, thereby hailing the imminent age of intestine transplants.

In 2004, the doctors who did tube baby experiments for a patient in Chicago known to have a genetic disorder started to produce a series of stem cells from generated embryos. They made models at the cellular level of the emergence of such genetic disorders as thalassemia, Huntington’s disease, Marfan syndrome, and muscle dystrophy. In 2007, they used embryonic stem cells to suppress molecular changes that trigger mental disorders caused by a genetic disorder called fragile X syndrome.

Research shows that multipotent (mesenchymal) cells stimulated at the outset of tissues are even more promising than embryonic cells with respect to diseases because it is easier to repair damaged or missing tissue by guiding them. However, it is essential in a genetic disorder that cells derived at the beginning of the embryonic stage should be used in order to replace faulty genes with healthy ones and address the disorder at its outset.

Experiments are underway that aim to treat disorders by activating stem cells stored in the body that have not yet differentiated through the help of proper stimulating molecules. In this way, as many as ten illnesses are likely to be treated, some of which include diabetes, macular degeneration in the eye, and neurodegenerative diseases such as Parkinson’s.

Douglas Melton from Harvard Stem Cell Institute in Cambridge has worked for fifteen years to transform embryonic stem cells into insulin-producing β-cells. He has produced pancreatic cells that sense glucose and produce insulin and he hopes to transplant them to end the dependence of patients of diabetes type-1 on insulin shots. The last obstacle remains to be the introduction of these cells to the system so that they are not destroyed by the patient’s immune system.

Clinically, it is believed that stimulated multipotent cells have a greater advantage than embryonic cells because the produced cells and tissues have the same DNA as the patient and thus do not cause any immune reaction when they are transplanted. The problem for many genetic disorders including type-1 diabetes is that the patient has the same mutation in his or her genes, and a method should be devised for cleaning and replacing these cells.

Another problem is the cost. It is reported that preparation of a series of multipotent cells will cost about one million dollars. However, the cost is expected to decrease and cells will be developed for the treatment of Parkinson’s disease, which is caused by a loss of neurotransmitter substance, which enable communication between nerves, and dopamine.

Treatment of macular degeneration is a popular target in this field. Patients gained the ability to read, though slowly, one year after the transplantation of part of stimulated multipotent cells to a damaged retina.

Such research studies normally cause some opposition. Playing with genes and embryos involve certain ethical and health risks. Yet, as reported in a Prophetic tradition, with all our God-given abilities like intelligence, curiosity, and willpower, humans can, and hopefully will, find cures for all diseases. Research into stem cells has the potential to provide many breakthroughs in these efforts to find healing for every human. Scientists and ethicists have to work together to determine our direction not to cause any unintended harm to any single soul while moving forward with this research.

Observing Majorana fermions in the ferromagnetic atomic chains on a superconductor. Nadj-Perge et al. Science, October 2014.

In the universe, matter and antimatter particles are always produced as a pair and, if they come in contact, they destroy each other in a flash of energy. In 1937, an Italian theoretical physicist named Ettore Majorana had proposed that there can be unique exceptions to this rule: a stable particle could exist in nature that is both matter and antimatter. Scientists have been looking for that indefinable particle, also known as the “Majorana fermion,” for seventy years. A group of researchers recently reported that they were able to detect the Majorana particle which behaves simultaneously like matter and antimatter. Researchers designed an experimental system allowing them to observe an emergent particle inside a material. They first generated an extended chain of pre magnetic iron atoms on a superconductor made of lead. Then, they cooled the material to -272 C, just about one point above absolute zero, and monitored it using a giant two-story-tall scanning-tunneling microscope, which can track electrical signal changes with very high precision. Finally, they were able to capture a glowing image of an electrically neutral particle at the ends of atomically thin iron wires. The Majorana particle was surprisingly stable and the opposing properties make the particle neutral so that it interacts very weakly with its environment. The discovery of the Majorana particle has exciting implications for several areas of modern physics, engineering, and astrophysics. For example, Majorana particles are very similar to neutrinos, as they both have very weak interactions with the matter. Neutrinos are thought to make up most of the dark matter that fill the Cosmos. Perhaps, neutrinos are simply Majorana-like particles and Majorana particles are also a candidate for what dark matter is. As an industrial application, Majorana particles can be utilized in quantum computing which aims to create computers to handle incalculable systems. The current quantum computing technology uses electrons, but they are known to be very unstable due to high interaction rates with surrounding materials. However, since Majorana particles are neutral and highly stable, they can be engineered into a variety of materials to produce more reliable and powerful quantum computing applications.

The Bitter Side of Artificial Sweeteners

Artificial sweeteners induce glucose intolerance by altering the gut’s microbiota. Suez J. et al. Nature, September 2014.

There have been conflicting and confusing findings about the health effects of artificial sweeteners over the past several decades. Some studies found that they cause weight loss and others found the exact opposite. Some studies linked them to diabetes and other studies argued otherwise. A recent study provided a series of experimental evidences that artificial sweeteners disrupt the body’s ability to regulate blood sugar, and thus may cause metabolic diseases and diabetes. Researchers, using animal models and human studies, found that sweeteners significantly alter the gut’s microbiome – the collective name of bacterial colonies living in our intestines. The composition of our gut microflora plays a critical role protecting us from pathogenic bacteria, the metabolism of indigestible components of our diet, and modulating development and regulation of the immune system. Sweeteners – in the form of saccharin, sucralose, or aspartame – are found to alter the mix of microbes in our intestines and consequently change how our bodies metabolize glucose. Constant use of sweeteners in mice and human test groups caused typical glucose intolerance symptoms in which glucose levels rose higher after eating and declined more slowly than expected. Glucose intolerance can ultimately lead to serious illnesses like metabolic syndrome and Type 2 diabetes. Although this study will cause a lot of discussions and headaches in the food industry, the link identified between microbiome and glucose intolerance will definitely inspire novel therapeutic approaches to metabolic disorders such as diabetes.

Brainy Fingertips

Edge-orientation processing in first-order tactile neurons. Pruszynski JA and Johansson RS. Nature Neuroscience, August 2014

A new study found that neurons in human skin are able to perform advanced calculations that scientists thought only the brain was capable of performing. A group of sensory neurons that extend into the skin and record touch are called first-order neurons in the tactile system. Each nerve ending branches in the skin to form about 5mm2 elliptical receptive field, with up to 8 highly sensitive zones that are unevenly distributed within the field. It turns out that these neurons not only transmit information about when and how intensely an object is touched to the brain, but they also send complex information about the touched object’s shape. Researchers found that the sensitivity of individual neurons to the shape of an object depends on the layout of the neuron’s highly-sensitive zones in the skin. Computations that require untangling geometric shape information are classified as feature extraction computations in neuroscience and are typically attributed to the immensely complex circuits of the cerebral cortex. This study showed that neuronal populations localized outside of the brain, such as first-order tactile neurons, can have advanced processing capacity similar to brain neurons. These results can also potentially improve treatments for nerve injury and rehabilitation, as scientists previously assumed that the cerebral cortex was doing all the work.

In recent years, people have been divided by conflicting studies about the risk of cancer posed by cell phone radiation. Does the current conflicting research eradicate or support the cell phone-cancer controversy?

Cell phone use has shown a dramatic increase in the world during the 1990s. The heated controversy today is about whether there is a relationship between cell phone use and the risk of developing malignant and benign brain tumors. This controversy did not exist—at least in the eyes of the public—until accumulating anecdotal evidence began suggesting a link between cell phone use and cancer. Since the first pieces of anecdotal evidence, numerous studies have investigated the cell phone-brain cancer link and a general summary of the findings is, at best, confusing. The substantial room for improvement in the experimental designs of these studies, the appearance of brain cancer after a long period of exposure, and some conflicts of interest among researchers prevented the results from being conclusive. More recent studies provide growing evidence for the link, suggesting there is reason to be suspicious about the studies that refute the relationship between cell phone use and brain cancer.

Possible health issues regarding exposure to radio frequency (RF) energy were described in a previous Fountain article (Tombak, 2002). This article also stated that proving or disproving the existence of RF exposure’s biological hazards remains an issue for epidemiology due to relatively low exposure levels, relatively small populations, and a lack of reliable dose estimates. The National Cancer Institute (NCI) is now maintaining an up-to-date web page to inform the public on key points that can be drawn from epidemiological studies investigating the cell phone-brain cancer link. It would be advisable that individuals concerned about this potential link become familiar with this web page and visit frequently to check the updates. A regular visitor will notice that the language on this page is evolving in every update in a way that the most recent version is less likely than the previous one to discredit the link as “out of the question”. This is because we are starting to see—albeit still opposed as weak—stronger signs of the alleged link as there is an increase in both the sheer number and the experimental design quality of relevant studies.

The first two key points that NCI draws on concern the type of electromagnetic energy emitted by cell phones, and the factors that determine a users energy exposure level. It would not be surprising if this train of thought followed with a third key point that stated that the cancer risk depended on the amount of energy that each individual was exposed to. However, the third key point quickly draws the conclusion that “studies thus far have not shown a consistent link between cell phone use and cancers of the brain, nerves, or other tissues of the head and the neck.” It further states “more research is needed because cell phone technology and how people use cell phones have been changing rapidly”.

Regardless of what type of general message one gets from these three key points, I want to emphasize that there is benefit in avoiding a lump-sum conclusion, and in making oneself aware of the results of individual studies. Before I move on to individual studies, however, I will point out how scientifically sound interpretations of statistical power and significance may lead to categorizations as ‘non-existent’ or ‘weak’, but how this scientific reasoning can potentially be misleading for the population at large. In this manner, one would better be able to make sense of why cell phone companies are, on one hand, highlighting the studies that have failed to find a causal link between cell phone use and brain cancer, but on the other hand, are taking all legal precautions necessary to prevent a future litigation by inserting a warning slip in fine print that cautions users not to hold the phone closer than a certain distance against one’s head or body.

The null vs. the alternative

A statistical hypothesis test involves two hypotheses: the null and the alternative hypothesis. The null hypothesis represents the status quo; it assumes that there is no real difference between the two groups under study and the observed difference can be attributed to random chance. Drawing a parallel with legal systems, the presumption that a defendant is innocent until proven guilty can be interpreted as saying that his or her innocence is the null hypothesis. There has to be sufficient evidence on the contrary, i.e showing the guilt, in order to be able to convict the defendant. In a similar fashion, an epidemiological study investigating the presence of a link between cell phone use and brain cancer would have a null hypothesis that states the absence of such a link. The cell phone technology is assumed to be innocent unless the data prove otherwise.

The alternative hypothesis, the latter of the two, represents the claim that there actually is a statistically significant link between cell phone use and brain cancer, and the observed link cannot be attributed to random chance. In our legal analogy, the alternative hypothesis is laying the charges against cell phone technology, thus as the Latin maxim “semper necessitas probandi incumbit ei qui agit” states, the burden of proof lies with the alternative hypothesis.

As a consequence of this construction, a hypothesis test can have only one of two conclusions. If the data shows results that are beyond some predetermined significance level, the null hypothesis is rejected and the researchers believe that there is sufficient evidence to say that the alternative is true. Such a conclusion would establish a link between cell phone use and brain tumors. On the other hand, if the results do not reach the desired significance level, the conclusion is not the confirmation of the null hypothesis, but a failure to conclude that the alternative is true. In other words, when the desired significance level is not reached, the only outcome is a lack of conclusion; the test would not falsify the null hypothesis but would not declare it to be true either. The accused would be vindicated on the basis of insufficient evidence.

News on the innocence of cell phone technology, or any technology for that matter, should be read primarily with this perspective in mind. The conclusions of research studies are reported on the basis of whether the results “reach or fail to reach significance”. However, a more meaningful statistic to report from the study would be the deviation of the results from significance, if they were not significant. Results that are close to statistical significance can still be “meaningful”. After all, the significance level chosen for most studies relies more on traditional scientific habits than anything else. In this perspective, it can even be called arbitrary. In reality, we may not have expertise in today’s world to determine whether a 5% significance level is more meaningful than a 10% when it comes to studying the link between cell phone use and brain cancer. So when the NCI officials mention “lack of a consistent link,” all of what they mean is that the desired significance level has not been reached in most credible and up-to-date studies. Yet, the public is not informed about how significant the results were. Furthermore, as we see in the much-acclaimed Interphone study, failure to reach significance in the entire study may be overshadowing the fact that significance was attained for a subgroup of people, for instance, the top 10% of the population with highest cell phone use (The Interphone study group, 2010).

Perspectives on brain cancer risk

News regarding cell phone tumor risks is plainly confusing because a battle continues among different international panels and interest groups over how to analyze and interpret cell phone tumor data. An article (July 6, 2011) on Microwave News explains why there is no overlap in the conclusions made by the International Commission for Non-Ionizing Radiation Protection (ICNIRP) and the International Agency for Research on Cancer (IARC), the two panels that are supposed to work together, but fell into deep disagreement as the data started showing some link between cell phone use and brain cancer. This piece is a highly suggested read for anyone who would like to be able to make more sense of the past and potentially future news on cell phone tumor risks.

The Interphone study

Much of the current debate on cell phone tumor risks actually revolve around the Interphone study, which was conducted by a consortium of researchers from 13 countries, and is the largest health related case control study of the use of cell phones and head and neck tumors. According to NCI’s summary, “most published analyses from this study have shown no statistically significant increases in brain or central nervous system cancers related to higher amounts of cell phone use. One recent analysis showed a statistically significant, albeit modest, increase in the risk of glioma among the small proportion of study participants who spent the most total time on cell phone calls. However, the researchers considered this finding inconclusive because they felt that the amount of use reported by some respondents was unlikely and because the participants who reported lower levels of use appeared to have a reduced risk of brain cancer.”¹

The general message that comes across in NCI’s summary of Interphone results is that we do not have enough reason to believe that cell phones are dangerous. However, it is very important to remember that one can never accept the null hypothesis that “cell phones are safe.” The only conclusion that can be drawn is on the basis of insufficient evidence, which is to say that cell phones are dangerous since the desired significance level has not been reached.

As the Interphone study is the largest of its kind, it has drawn substantial attention from concerned parties, and a significant part of this attention has been in the form of harsh criticisms for the experimental design, data analysis, and stated conclusions. For instance, one of Interphone’s biggest critics, the International Electromagnetic Field (EMF) Collaborative, published a paper in May 2010 detailing the flaws of the study. Among other things, these flaws included using data from 2004 and before when cell phone use was much less common, categorizing subjects who used cordless phones (which emit the same microwave radiation as cell phones,) as ‘unexposed’; exclusion of many types of brain tumors; exclusion of people who had died, or were too ill to be interviewed, as a consequence of their brain tumor; and exclusion of children and young adults who are more vulnerable.

In August 2009, more than forty leading independent scientists, physicians and other experts from fourteen countries endorsed the white paper “Cell-phones and Brain Tumors: 15 Reasons for Concern, Science, Spin and the Truth Behind Interphone” by US researcher Lloyd Morgan. Investigating the research on cell phone tumor risks including the Interphone study, this paper concluded that “there is a risk of brain tumors from cell phone use; telecom funded studies underestimate the risk of brain tumors; and children have larger risks than adults for brain tumors”. Unlike the Interphone study, some industry funded research also accepts the risks associated with cell phone use. In 1999, Dr. George Carlo, head of a $25m research body funded by the mobile phone industry in the US, said his study showed an increased risk of getting a type of rare brain tumor from using mobile phones. This early in the debate, he was probably one of the first researchers with links to industry who stopped ruling out the tumor risks of cell phones.

A review of other main studies

Hardell et al.

Dr. Lennart Hardell, from Örebro University in Sweden, is one of the most adamant leaders in cautioning the world about cell phone tumor risks. In 2007, he and his team reported that cell phone users were at an increased risk of malignant glioma, and that a daily one-hour exposure significantly increased the risk for developing a brain tumor after 10 years (Hardell et al., 2007). In a more recent study also cited by NCI, they found statistically significant trends of increasing brain cancer risk for the total amount of cell phone use and the years of use among people who began using cell phones before the age of 20 (Hardell et al., 2011). They also published a number of other papers in epidemiological journals pointing to the risks associated with cell phone and cordless phone usage.

The Danish cohort study

A 2011 cohort study in Denmark linked billing information from more than 420,000 cell phone subscribers with brain tumor incidence data from the Danish Cancer Registry (Frei et al., 2011). This study was an update on the 2006-update of a 2001 cohort study (Schüz et al., 2006; Johansen et al., 2001) that has been dogged by controversy and political suspicions since the first results were published ten years ago. NCI cites the study and states that the analyses found no association between cell phone use and the incidence of glioma, meningioma, or acoustic neuroma, even among people who had been cell phone subscribers for 10 or more years. However, there is no mention of the published or vocal criticisms of the study.

The main criticism for the study is that more than 200,000 corporate mobile subscribers were excluded from the cohort as cell phone bills were not in users’ names. Microwave News states, “In the time period covered in the Danish project—from 1987 through 1995—cell phones were expensive and it’s no stretch to assume that those who did not have to pay their own bills racked up the most talk time.”² Thus, the study designers effectively removed one-third of the population with the heaviest cell phone use. Dr. Lennart Hardell had also criticized the original 2001 paper by publishing on the shortcomings that make the conclusions premature (Hardell and Mild, 2001). Concerning the 2011 update, the Microwave News bluntly suggests, “Don’t believe a word of it”.

It is also interesting to note that the results came just five months after a panel of experts from the World Health Organization’s International Agency for Research on Cancer (IARC) deemed cell phones a possible cause of cancer—a statement that sparked fear in many of the world’s 5 billion cell phone users.

Conclusion

While there is still no established causal link between cell phone use and cancer, we know as a fact that different research groups have found an increased risk of a rare type of brain cancer among heavy users. Even though children are known to be at a greater risk because of being in earlier stages of neural development, it is unfortunate that data from children were not included in studies until very recently. Concerned citizens of the world need to raise awareness about the behind-the-scenes battle taking place between different international panels and interest groups. This will make a reliable interpretation of conflicting news more possible. Further corroboration for both statistical and anecdotal evidence on the relationship between cell phone use and brain cancer may be necessary to “prove” a link, but this should, by no means, be interpreted as a vindication of cell phones. In the meantime, it is only safe to take precautions oneself, and encourage loved ones to reduce exposure to electromagnetic energy from cell phones by using a hands-free device and by reserving the use of cell phones for shorter conversations.

Notes

1 http://www.cancer.gov/cancertopics/factsheet/Risk/cellphones

2 http://www.microwavenews.com/DanishCohort.html#Continued

References

• Frei P, Poulsen AH, Johansen C, et al. 2011. “Use of mobile phones and risk of brain tumours: update of Danish cohort study.” British Medical Journal; DOI: 10.1136/bmj.d6387.
• Hardell, L., Walker, M. J., Walhjalt, B., Friedman, L. S. and Richter, E. D. 2007. “Secret ties to industry and conflicting interests in cancer research.” American Journal of Industrial Medicine,; 50: 227–233. doi: 10.1002/ajim.20357.
• Hardell L, Carlberg M, Soderqvist F, Hansson-Mild K, Morgan LL. 2007. “Long-term use of cellular phones and brain tumours: Increased risk associated with use for > or = 10 years.” Occup Environ Med. 64:626–632.
• Hardell L, Carlberg M, Hansson Mild K. 2011. “Pooled analysis of case-control studies on malignant brain tumours and the use of mobile and cordless phones including living and deceased subjects.” International Journal of Oncology; 38(5):1465–1474.
• Hardell L, Mild KH. 2001. “Re: Cellular Telephones and Cancer—a Nationwide Cohort Study in Denmark”; JNCI J Natl Cancer Inst. 93(12): 952.
• Johansen C, Boice Jr. JD, McLaughlin JK, Olsen JH. 2001. “Cellular telephones and cancer: a nationwide cohort study in Denmark.” Journal of the National Cancer Institute; 93(3):203–207.
• Schüz J, Jacobsen R, Olsen JH, et al. 2006. “Cellular telephone use and cancer risk: update of a nationwide Danish cohort.” Journal of the National Cancer Institute; 98(23):1707–1713.
• Tombak, Ali. 2002. “Biological Effects of Cellular Phones.” The Fountain, 37 (1).
• The Interphone Study Group. 2010. “Brain tumour risk in relation to mobile telephone use: results of the Interphone international case-control study.” International Journal of Epidemiology; 39(3):675–694.

In spite of the developments in science and technology, we are still so powerless at predicting phenomena; there is so little we can control and uncertainties are so many. We do not face the challenge of uncertainties at predicting happenings but also at decision-making. While we make decisions in daily life we try to minimize uncertainties. Any decision that holds uncertainties in its nature is risky. Therefore, decision-making processes are a kind of risk management at the same time. All the efforts are directed toward reducing the possible risks and mistakes. High-risk problems have a higher ratio of mistakes.

Studies of forecast need collecting numeric data and analyzing them along with obtaining relevant information based on observations. The data to be collected should be objective and the statistical methods appropriate. Otherwise, unsuccessful forecasts will lead to waste of time, money, and resources. Decision problems with uncertainties can be of different nature. For example, it is possible to reckon when an apple which broke off from its branch will reach the ground by knowing physical laws. As factors get more complicated, possibility of surprises is much higher. The discipline which systematizes these studies is econometrics. Statistics, mathematics, economics, optimization, decision-making, and computer science fall within the studies of econometrics. Forecast problems are mainly studied with numeric and extrapolative analyses.

In recent years, intuitive methods have been added to these two major approaches. Along with other issues, numeric analysis is frequently used in artificial neural networks, computer simulations, and computer-based learning methods. Artificial neural networks are formed by trying to model the millions of neurons in human brain work. The artificial cells whose number varies between five to ten are educated by using a certain mathematical transformation function, with recurring algorithmic processes. At the end of the process of education with past data, the performances of the calculations in new situations are evaluated. This method, which is used at various forecast problems, is really meaningful in terms of reflecting what can be done by merely copying a few of the millions of human nerves. However, the greatest obstacle before the studies of artificial neural networks are the computers with insufficient capacity. Even super computer systems have difficulty in an optimization problems with more than a hundred cells and the data obtained is far from useable. One cannot help but amaze at the perfect capacity of human brain and how it tackles hundreds of parallel processes incessantly. In some decision-making problems, due to insufficient numeric data, the parameters targeted to be forecast may not be reliable and present a peculiar nature. The studies about very rare diseases and forecasting technological developments are examples to that. In such cases, numeric analyses do not help because of not having any reliable numeric data. Therefore, extrapolative analysis methods are preferred at such forecast problems. At forecasts based on extrapolation, the expert’s level of knowledge, intuition, experience, capacity of processing information, and power of judgment are important but they remain limited. There are lots of forecast problems about socioeconomic life such as economic fluctuations, price moves, and commercial size. Healthy forecasts on how and when to make investments are very important in order for the investors’ determining how to utilize their resources. However, the investors’ decisions will inevitably have uncertainties to a great degree. Therefore, it can be said that studies of forecasting are still in the cradle.

No matter of what quality, forecasts are always needed, since expectations for the future need to be determined and met. One of the basic assumptions of the economic system that make its effect felt in the global scale is that, human beings are self-centered creatures who act on opportunist drives. Such philosophies have always impelled people to be egocentric. However, people can listen to their conscience instead. They can simply choose to be altruistic; they can choose to care about others and help them. It is possible to reverse such an understanding of selfishness by giving charity and fulfilling other responsibilities. Thus, the forecasts about the future depend on what is to be given priority. In other words, the science of forecast can serve a more humane philosophy.

Everything is finely balanced with appropriate measures in this universe. Everything is created with wisdom. From the perspective of forecasting studies, our efforts can in a way be seen as guesswork to learn about destiny. Although we can try to make predictions within certain limits, we can never ignore possible surprises which take place totally out of our control. Human beings are equipped with an ability to make decisions in the face of uncertainty. We are supposed to comprehend the philosophy of creation and try to discern the meaning of the pattern being woven by Providence.

Ertugrul Deniz is a freelance writer from Turkey with a PhD degree in mathematics.

References

• Makridakis, Spyros; Wheelwright, Steven; Hyndman, Rob J. (1998). Forecasting: methods and applications, New York: John Wiley & Sons.
• Fama, Eugene (1970). “Efficient Capital Markets: A Review of Theory and Empirical Work”. Journal of Finance 25 (2): 383–417.

In the past few decades many studies and articles on the subject of religion, spirituality and health, from both Western and Muslim perspectives, have been published. In this book, Salih Yucel’s quantitative and qualitative studies support previous research findings which suggest that religion and health are not mutually exclusive and that there is clearly a positive correlation between prayer and wellbeing.

This book comprises a research study taken from the author’s doctoral thesis, The Effects of Prayer on Muslim Patients’ Well-being. Also included in this book is a qualitative study which contains examples of many case histories and anecdotal evidence from Muslims who have benefited from the healing power of prayer, which includes salat (Islamic ritual prayers), dua (formal and informal supplication to God), and dhikr (remembrance of God, based on the Sufi concept of connectedness to the universe. Also included are Bediuzzaman Said Nursi’s “twenty-five remedies” for the sick which explains the concept of illness and how Muslims should view it in the light of belief.

The aim of this research has been to investigate the physical and spiritual effects of prayer on Muslim patients. Sixty adult Muslim in-patients, consisting of equal numbers of women and men from different educational backgrounds and nationalities, were recruited from the patient population at Brigham and Women’s Hospital, a Harvard Medical School-affiliated institution in Boston, Massachusetts. The research included a pre-test questionnaire in order to assess the spiritual level of the patients and a post-test questionnaire after prayers were completed. The surveys were based on Islamic sources, with the second survey split into two sessions: the first contained readings from the Qur’an while the second consisted of texts from a non-religious source, serving as a control in order to determine the effect of prayers on the patients.

Unlike previous studies, this research has provided guidelines for prayer which is based on the Qur’an, the Prophetic Traditions and the works of a number of Muslim scholars. The guidelines are a reminder that prayers should if possible be carried out under certain conditions, which include both physical and spiritual preparation prior and after prayer. Examples include taking ablution and ensuring clothes are clean prior to prayer and so on. Also some of the spiritual advice is extremely helpful, such as the understanding that prayer will always be answered but not necessarily in the way that individuals may expect it, thus reducing the disappointment patients may feel if they do not get exactly what they have asked for after prayer. However, other conditions, such as offering prayer “sincerely,” may not be so easy to ensure.

The findings of the preliminary survey were used to determine the level of religiosity/spirituality of patients from an Islamic perspective. These findings were consistent with previous studies, showing a strong correlation between religiosity/spirituality and hopefulness/confidence. The post-test survey based on self-report measures of religiosity and wellbeing following the prayer session also showed higher scores in comparison to the control group. With regard to vital signs and the positive physical effects of prayer on health, however, the data was not considered to be clinically significant. The author admits to some of the limitations of the study such as the hospital environment itself which is not conducive to prayer conditions. One of the main limitations has been the omission of compulsory prayers (salat) from the survey, as many bed-ridden patients were unable to take part in this activity. A longitudinal study with a larger participant group and a more convenient environment might possibly have produced better results.

However, the qualitative study included in this book, which consists of many case studies of people who have benefitted from the healing power of prayer, provides further support for the importance of including prayer as part of treatment. The main strength of the book lies in its approach, which is based mainly on Said Nursi’s ideas of remedies for the sick. These remedies enable patients to move away from reliance on the realm of causality and are able potentially to empower them to try to understand their condition in a much broader context that includes the concept of the Hereafter.