In 1981, scientists discovered ways to derive embryonic stem cells from early mouse embryos. Since then, they have been the subject of intense scrutiny, controversy, and advocacy.

They are unique cells, which can be derived from human embryos and can be differentiated into virtually any kind of different cells. In humans, there are about 200 different types of cells including bone, muscle, and nerve cells, and within these cells there are about 20 different types of structures or organelles. Essentially, stem cells can be derived from human embryos, and with the right enzymes, can be stimulated. For instance, bone cells can originate from osteocyte cells, or liver tissues can come from hepatocytes.

Stem cell types and research

There are three types of stem cells:

• Embryonic stem cells
• Adult stem cells
• Induced Pluripotent Stem Cells (iPSC)

Embryonic stem cells are derived from human embryos. Adult stem cells are undifferentiated cells (meaning “clean slates” with the potential to change into another cell variant) found throughout the body after development; they multiply via cell division to replenish dying cells and regenerate damaged tissues. Induced Pluripotent Stem Cells (iPSC), which were discovered in 2006, are derived from skin or blood cells that have been reprogrammed back into an embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes. While these types of cells are interesting and certainly worthy of research, this article will focus on embryonic stem cells as they are consistently the most well-known and discussed type by the general public.

Embryonic stem cells are potent and often sought after due to their abilities to proliferate without limit and contribute to any cell type. However, with great power comes great responsibility and stem cells are no exception. Poorly processed cells have been documented to mutate into cancerous tumors that can wreak havoc upon people’s bodies. Bearing this in mind, scientists also do not believe that this should derail stem cell therapies considering that there are DNA tests to check if stem cells will turn out to be problematic or not.

The stem cell project is regularly a subject of ethical debate in both the academic and public sectors. Most embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitro—in an in vitro fertilization clinic—and then donated for research purposes with the informed consent of the donors. People willingly donate their eggs for this research, and this process does not constitute child-killing since the eggs are near their zygote phase, not a whole mature embryo. Scientists obtain those types of cells from an embryo which has not yet completed its formation to develop into a human being. Researchers then use these cells for various treatment and research purposes. It is important to stress that they are not derived from eggs fertilized in a woman’s body and that they are produced in a plastic laboratory culture via clinics in vitro.

Some examples of embryonic stem cells being used in research include the following:

1. UCLA stem cell gene therapy cures bubble baby disease

Researchers at UCLA (University of California, Los Angeles) have developed a cure for babies born with Bubble Baby Disease, a rare and life-threatening condition that can be fatal within the first year of life, by using stem cells from multiple patients and gene therapy to correct the genetic mutation of these patients.

2. Asterias biotherapeutics restores some independence to those suffering from paralysis caused by spinal cord injuries

Asterias Biotherapeutics spent much of 2016-2017 developing a stem cell therapy to restore upper body motor function to quadriplegic spinal cord injury victims. Through lengthy and rigorous testing in human clinical trials, the therapy was found to be safe for use in people with all patients treated reporting at least some improvements. Asterias is now expanding its clinical trials to include patients with sub-acute injuries.

3. UC Irvine scientists engineer stem cells to destroy cancer

In a study conducted by University of California, Irvine researchers, a stem cell-based technique was devised to find and destroy breast cancer cells that had already metastasized. The cells “feel” the stiffness of the surrounding tissues and destroy the cancer-causing cells.

Embryonic stem cells can remain undifferentiated when they are grown in a well taken care of culture that is under stable conditions. Problems primarily begin to arise if cells are allowed to clump together to form embryoid bodies in which they begin to differentiate, or change into more specific cell variants, spontaneously. Although spontaneous differentiation is a good indication that shows which cultures of embryonic stem cells are healthy, the process is uncontrolled and, therefore, an inefficient strategy to produce cultures of specific cell types.

The ability of stem cells being able to differentiate into hundreds of other types of cells continues to amaze scientists as this is no small discovery. Researchers believe that the possibilities with stem cells are near endless, especially in regard to “regenerative medicine,” the process of “replacing, engineering, or regenerating human cells, tissues, or organs to restore or establish a new function.” It is even believed that even whole organs could be synthetically grown by using them.” Additionally, stem cells have the potential to rebuild healthy tissues, help people with heart disease, diabetes, ALS, Alzheimer’s disease, liver disease, Parkinson’s disease, cancer, and many more illnesses.

In a stem cell transplant, embryonic stem cells are first specialized into the necessary adult cell type. Then, those mature cells replace tissue that is damaged by a disease or injury. This type of treatment could be used to:

• Replace neurons damaged by spinal cord injury, a stroke, Alzheimer’s disease, Parkinson’s disease, or other neurological problems.
• Produce insulin that could treat people with diabetes and heart muscle cells that could repair damage after a heart attack
• Replace virtually any tissue or organ that is injured or diseased.

Sometimes scientists use stem cells as a drug. For example, it is possible to inject a stem cell into joints to reduce swelling and pain, or in order to promote the healing processes of soft tissues. Stem cell therapy is performed by injecting the patient’s own stem cells to stimulate the body to repair and replace damaged tissue in any joint or soft tissue structures – such as knees, shoulders, hips, wrists, ankles, elbows, tendons, ligaments and non-healing bone fractures. Cellular Dynamics, a large biotechnical company, sells human heart cells called cardiomyocytes that are derived from induced pluripotent stem (IPS) cells. Pharmaceutical companies are adapting to this new and innovative trend on a day-to-day basis. Stem cells can also be used to test the quality and safety of investigational drugs by testing them on stem cells that have been transformed into tissue-specific cells. Researchers are able to monitor the side effects before exposing the drug to a patient and thus have a greater expectancy of how their body may respond to the drug. This allows us to test for cures for potentially fatal diseases in ways that would otherwise be risky or unethical.

With all of the aforementioned advantages, stem cells are a fairly new, but exceptionally promising, research area. For some people, it may seem unethical to use stem cells on the grounds that extracting stem cells damages the blastocyst, which is a structure formed in the early development of mammals, more specifically the sixth or the eighth day of the development of an embryo. In 2006, President Bush vetoed the Stem Cell Research Enhancement Act stating that the federal government should not support “the taking of innocent human life.” Although stem cells are very promising for science and can open new doors to many new treatments in the medical field, it looks like there are still differences of opinion on their ethical use. This is perhaps because there is need for more convincing evidence or people are not informed accurately on the details of this research area.

References

• https://stemcells.nih.gov/info/Regenerative_Medicine/2006Chapter1.htm
• https://www.healthline.com/health/stem-cell-research
• https://www.statnews.com/2017/04/26/stem-cells-cancer-mutations/
• https://plato.stanford.edu/entries/stem-cells/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398703/
• https://www.mayoclinic.org/documents/the-amazing-stem-cell/doc-20249792
• https://www.unmc.edu/stemcells/educational-resources/history.html
• https://www.cirm.ca.gov/patients/power-stem-cells
• https://www.nature.com/news/stem-cells-take-root-in-drug-development-1.10713
• https://hsci.harvard.edu/examining-ethics-embryonic-stem-cell-research#:~:text=Opponents%20argue%20that%20the%20research,taking%20of%20innocent%20human%20life.%E2%80%9D

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.

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.

What are the basic traits that a teacher should have to be able to help students attain necessary language skills and cultural knowledge in an L2? As language educators, we receive this question all the time. Unfortunately, the answer to this question is not an easy one because research involving curriculum analyses, both in the United States and in Europe, has revealed a significant amount of variation in the number of domains and competencies covered in L2 teacher education programs (Richards, 2008). While some programs have predominantly focused on language and L2 acquisition research and theory, others have taken a more linguistics and methods-orientated direction. In general, though, most experts in the field would agree on a number of fundamental competencies.

Competent L2 teachers know who their learners are (1), what language is (2), how it is learned (3), and how it should be taught (4). Furthermore, they have a solid background about the foundations of L2 curriculum (5), the selection and development of instructional materials (6), and the design of a learning environment (7) that is sensitive to socio-cultural differences (8). They also know how to use the L2 as a tool for L2 learners to gain access to academic content knowledge (9). While they are also able to situate the whole language learning and teaching experience within broader learning theories (10), and competently assess and evaluate L2 development and proficiency (11), they are well aware of their professional roles and responsibilities as advocates for successful L2 education in its entirety at all levels, including institutional, national, and international. Indeed, these competencies have been categorized under the five domains of (I) Language Learning, (II) Learners, (III) Instruction, (IV) Assessment and Evaluation, and (V) Professionalism and Advocacy. Before any further ado, let’s take a look at what each competency entails.

Domain I: Language learning

This domain includes background knowledge and skills in (1) linguistics, (2) general learning theories, and (3) first and second language acquisition theories. First, L2 teachers need to be highly proficient in the language that they teach. Competent L2 teachers understand the nature of language and basic concepts of language systems such as phonology, morphology, syntax, lexicon, semantics, discourse, and pragmatics. They are also familiar with socio-linguistic, psycho-linguistic, and neuro-linguistic factors in L2 learning. Furthermore, they know the functions and register of the L2, including the conventions of written and spoken language, and the pedagogical implications of differences between basic interpersonal communication skills (BICS) and cognitive academic language proficiency (CALP) (Cummins, 1984). In addition, they understand the interrelatedness of receptive (listening, reading), productive (speaking, writing), and complementary (grammar, vocabulary, pronunciation) language skills.

Second, competent L2 teachers are familiar with the basic theories and concepts about first (L1) and L2 acquisition, including the language universals (Chomsky, 1965), and the role L1 plays in L2 development. While they understand differences between the processes of L1 and L2 acquisition, they have a solid background in second language acquisition (SLA) theories. For example, they know how to use different ways to maximize the comprehensible input (Krashen, 1987) opportunities for their students through authentic tasks and activities. More importantly, they know that the greatest bulk of an L2 is acquired through self-exposure and social interactions, not learned in strictly structured and inauthentic classroom settings. Finally, competent L2 teachers are able to situate SLA theories within the broader learning theories. For instance, they understand behaviorist (memorization) versus cognitivist (information processing) versus socio-constructivist (socio-cultural factors) views (Pavlenko – Lantolf, 2000) about L2 learning and development.

Domain II: Learners

Current SLA research has revealed that socio-psychological factors affect success in learning an L2. This domain covers teacher knowledge about (1) differences among language learners and (2) their levels of socio-cultural awareness. Individual differences, such as motivation, attitudes, anxiety, identity, learning styles, pedagogical beliefs, socialization patterns, and learning and communicative strategies affect success in learning an L2. For example, many scholars have found that high motivation has a positive effect on L2 learning (Dörnyei, 2005) while learners with high levels of anxiety do not seem be successful language learners (Horwitz, 2008). In fact, researchers have found that learners who strongly identify with the L2 community attain a more native-like accent than those who strongly identify with their native-speaking communities Dörnyei – Ushioda, 2009). Competent L2 teachers know about the role these factors might play in L2 attainment and plan the learning experience for their students accordingly.

Other learner-related factors concern the socio-cultural differences. L2 learners come from different families and geographical regions with different socio-economic and educational backgrounds, demonstrating a significant amount of cultural diversity. Culturally responsive L2 teachers understand the role of diversity – namely cultural products, perspectives, and practices – in L2 attainment. They know not only how to construct culturally-sensitive learning experiences to facilitate the most effective learning, but also what strategies to apply to create among students an awareness of and respect for cultural diversity. Indeed, culturally competent teachers effectively apply skills for communicating and collaborating effectively with the parents/guardians, the community members, and local resources to enhance their students’ learning. For example, such teachers not only genuinely value cultural diversity and incorporate it into the curriculum, but also organize extra-curricular activities in appreciation of diversity as an added value for advancement.

Domain III: Instruction

Under this domain, we have instructional competencies including (1) foundations of curriculum, (2) methods of language teaching, (3) learning environment, (4) instructional materials, and (5) language and content area integration. First, competent L2 teachers know the history and policy foundations of L2 education and use this knowledge to plan and implement effective L2 programs (Richards, 2001). They are able to select the most effective types of programs that are appropriate for the needs of a particular learner profile in a particular setting. For example, while most scholars agree that bilingual and immersion programs are the most effective, the most common English as a second language (ESL) programs in the U.S. are the pull-out ones, also known as the least effective programs that are primarily based on the development of BICS skills while neglecting the teaching of CALP via content-based curricula.

Second, competent L2 teachers are also able to choose and implement the most appropriate and current methods of language teaching. Such teachers know that we have come a long way since the grammar translation and audio-lingual method (Richards – Rodgers, 2001), however, we no longer adhere to one particular method because we live in the beyond-methods’ era (Kumaravadivelu, 2006). Nonetheless, this does not imply a senseless, eclectic approach; rather it entails being flexible within a consistent theoretical and pedagogical framework often referred to as “principled eclecticism” (Larsen-Freeman, 2003). Third, as the current ecological L2 learning theories would suggest (Brown, 2006), just as only a balanced amount of sun, water and care, in a nurturing environment, can lead to the healthy growth of a flower, instructional methods can lead to success in L2 learning only if the learning environment is meticulously designed.

Last but not least, an important part of what constitutes a nurturing environment is the availability of effective instructional resources. Competent L2 teachers are not only well-informed about the strengths and weakness of commercial and authentic materials but also possess the necessary skills to select, adapt, or develop their own materials based on the specific needs and goals of their students. Indeed, competent L2 teachers use the instructional materials that integrate the language and content area goals, supporting L2 learners’ BICS, CALP, and academic achievement (Cummins, 1984). For example, most English-medium universities overseas have English preparatory programs to prepare students to be able to receive, say, engineering or economics content in English; however, instead of conducting a needs analysis and basing their EFL instruction on the content of these majors, most of these programs select generic commercial materials that often times include linguistic input predominantly about shopping, holidays, food, and friendship.

Domain IV: Assessment and evaluation

This domain covers knowledge and skills about the assessment and evaluation of L2 learners’ language development. It includes background in L2 testing skills related to the placement, diagnostic, achievement, and proficiency of L2 learners. Competent L2 teachers know the commonly used national and international standard assessment tools, such as TOEFL. Such teachers also know the basic concepts and practices related to test design, development, and interpretation. In addition to understanding the validity and reliability of testing methods and tools, they understand potential relationships among the national standards, instruction, and L2 testing. More importantly, in their classrooms, they effectively apply knowledge of formal/informal, direct/indirect, and dynamic and authentic assessment. Most importantly, however, competent teachers are familiar with the construct of the “backwash effect” – the effect testing might have on student learning (Hughes, 2003). Successful learning will not take place if teaching and testing goals and/or methods are incongruent. For example, if writing skills are tested by multiple choice tests, students will invest their time and effort in developing their skills to respond to such questions, not in working on actual writing skills that they will need in real-life tasks.

Domain V: Professionalism and Advocacy

As part of the last domain, L2 teachers are required to possess certain professional qualifications and individual characteristics to be able to support L2 learners’ linguistic, cultural, and academic development. This domain lies at the heart of the profession. Competent L2 teachers demonstrate knowledge of the history of L2 teaching, keep up-to-date with new trends and current educational research, and follow domestic and international issues related to language planning and policy, as well as other advances in L2 education. Moreover, considering language learners spend only a limited amount of time with language teachers, it is very important that L2 teachers collaborate with the mainstream teachers and build partnerships with outside resources and parents to support the linguistic, cultural, and content areas of development. Also noteworthy is that such teachers claim responsibility for L2 learners and are able to apply effective strategies to advocate educational and social equity for their students, both at the institutional and broader community levels (Crawford, 2004). For instance, such teachers serve as a resource to promote a school environment that values cultural and linguistic diversity, and they advocate for equitable access to resources for language learners by becoming members of organizations (e. g.: TESOL) that support L2 learning and teaching.

Furthermore, in order for teachers to apply these professional competencies in actual classroom practices, they need to posses certain individual characteristics and dispositions that complement their professional qualifications. Unlike learning other subjects, language learning requires a great deal of patience and perseverance. Hence, L2 teachers need to be caring, compassionate, understanding, self-sacrificing, and patient. They need to establish a good rapport and empathy with their students, offering them timely motivational support. Only by doing so can they understand their students’ socio-psychological well-being and invest additional personal time and effort in students’ learning.

Last but not least, L2 teachers need to remain positive and enthusiastic about their students’ progress, because the process of L2 development is a bumpy road with lots of ups and downs. To help their students, teachers need to be able to identify their students’ struggles correctly and provide them with developmentally appropriate support. In addition, they need to be fair and treat all of their students equally. In doing so, they need to know their students very well and think outside the box, supplying innovative in-class and self-study strategies. Finally, in order for L2 teachers to be able to competently demonstrate these personal traits, they need to have effective communication skills. While such teachers are very good and empathetic listeners, they also need to be able to communicate their thoughts and feelings effectively, and with mutual respect and appreciation, to support their students’ learning.

Saban Cepik is Assistant Professor/Department Chair, ELT, Zirve University.

References

• Brown, D. H. (2006). Principles of Language Learning and Teaching (5th Edition). New York: Pearson ESL.
• Chomsky, N. (1965), Aspects of the Theory of Syntax. Cambridge, Massachusetts: MIT Press
• Cummins, J. (1984) Bilingualism and special education: Issues in assessment and pedagogy. Clevedon, England: Multilingual Matters.
• Crawford, J. (2004). Educating English Learners: Language Diversity in the Classroom. (5th ed). Los Angeles, CA: Bilingual Education Services.
• Dörnyei, Z. (2005). The psychology of the language learner. Mahwah, NJ: Lawrence Erlbaum.
• Dörnyei, Z. – Ushioda, E. (Eds.). (2009). Motivation, Language Identity and the L2 Self. Bristol: Multilingual Matters.
• Horwitz, E.K. (2008). Becoming a language teacher: A practical guide to second language learning and teaching. Boston, MA: Allyn – Bacon, Inc.
• Hughes, A. (2003). Testing for language teachers. Oxford: Oxford University Press.
• Krashen, S.D. (1987). Principles and practices in second language acquisition. New York: Prentice-Hall.
• Kumaravadivelu, B. (2006). TESOL methods: Changing tracks, challenging trends. TESOL Quarterly, 40, 59-81.
• Larsen-Freeman, D. (2003). Teaching language: From grammar to grammaring. Boston: Thompson-Heinle.
• Pavlenko, A., – Lantolf, J. P. (2000). Second language learning as participation and the (re)construction of selves. In J. Lantolf (Eds.), Sociocultural theory and second language learning: Recent advances (pp. 1545-177). New York: Oxford University Press.
• Richards, J. C. (2001). Curriculum development in language teaching. NY: Cambridge University Press.
• Richards, J. C. (2008). Second language teacher education today. RELC Journal, 39: 158-177.
• Richards, J., – Rodgers, T. (2001). Approaches and methods in language Teaching (2nd ed.). Cambridge: Cambridge University Press.

Culture as we know it is generated from thoughts, emotions, attitudes and behaviors, networks of symbols, values, beliefs, and sensory perceptions. Culture itself also changes, differs and is transferred among generations. Memetics is a new field of science that tries to understand questions such as How does the mind work? How do humans learn and develop? How does culture form and transfer to future generations?

One of the major tenets of memetics is the meme, or meme concept. The meme concept is assumed as a mental unit to understand the structure and function of culture. Symbols (imaginations), cognates, archetypes, images, concepts, values, beliefs, emotions, attitudes, and behaviors that are produced inside the human mind are either memes or a meme set. Memes are described as mysterious codes of behavior, and the main production unit of reality and function of the human mind. Concepts like mind, cognition, and memory as well as the functioning of the genes and viruses have been instrumental in the development of the meme.

If we consider the human brain as a computer, genes can be regarded as units that make up the hardware, and memes as units for software. Speech and language skills enable the formation and transfer of memes that build mind and culture. Forms of literature and different sciences are also memes that help define a specific culture and civilization. It is accepted that memes are units that code, reproduce, and store ideas, emotions, and behaviors.

Since memes can only be reproduced in the mind and transferred via the brain’s activities, they are also described as the viruses of the cultural world. The common feature of biological and computer viruses is that they leak into the system by concealing themselves, and thus infect other structures in the medium by replicating there. Through memes, acting as agents (viruses) that reproduce and diversify ideas, culture is transferred via media, speech, and mass communication devices. One such example of this would be commercials. Commercials and other forms of advertisements are produced by utilizing powerful memes.

Genes and the laws of genetics help us to understand memes. Genes and memes are very similar to each other in terms of working principles. Just like genes, memes are also multidimensional and multifunctional. The roles that genes play in the biological world are similarly carried out by memes in the mind. There are regulatory memes, just like regulatory genes. There are immunoglobulin genes in charge of protecting against diseases, just as there are memes that guard against bad, harmful, and unwanted cultural practices. Ethical teachings, decency, the concept of right and wrong, lawful and unlawful are examples of memes that conserve a culture’s spiritual and ideological world.

Genes have helped the brain to develop in such a way that they store and reproduce memes. The synapses and neural networks of the brain are drawn towards certain memes. Neural genes and their products (neurotransmitters, neural networks and synapses) work in conjunction with these memes, spreading their content.

Knowledge is spread in this way. Like unlocking a door is dependent on a complete match and fit of the key and lock, the production, storage, reproduction, and transfer of memes relies on fitting with the proper genes. In other words, there is a high level of adaptation and association in between memes and memetic structures that are encoded into the structure of the brain. Therefore, not every meme can find its place in each mind; likewise, not every brain can accommodate and propagate all meme forms. This relation explains both why humans have different interests and respond differently to the same stimulant. In the meantime, it sheds light on the role of memes in the development of different mentalities, perceptions, and opinions.

Just as genes affect memes, memes also affect genes. Memes that form in the mind play a role in the expression, regulation, and control of genes. Memes such as emotions and ideas lead to alterations in the electrical activities of the brain. Furthermore, this triggers the excretion of neurotransmitter materials and the synthesis of transcription factors that switch gene activity on and off. Some of these memes can be pleasant, or they may be unwanted and disturbing. Thus, there is also a need for anti-memes, in order to neutralize unwanted and disturbing ones.

Belief systems, and conversely non-belief, produce different memes and this difference causes variations in a person’s neural gene activity. The mental processes of a person possessing right or wrong memes shaped by religious faith will not be the same compared to a person who does not have these memes. This is similar to the way a person with positive and joyful memes sees life in a different light than someone who has negative and harmful memes.

The task that antivirus programs have in the computer world is similar to the tasks of anti-memes in our mind. Of course, a person can influence this process through willpower. Good things represent nice and pleasant memes and wrong ones symbolize unwanted and harmful memes. Of course, each country or culture has different definitions of what is good and what is wrong. From this perspective, so-called “culture wars” are actually wars of memes and memetics. It is only possible to understand civilizations through analyzing the algorithms and memetic maps which were used to erect them.

Memes are investigated under three main groups according to the anatomical and functional structure of the brain. The first is memes that are stored and populated in the neocortex, which is associated with advanced mental functions such as willpower, consciousness, and intangible thinking. These memes are also defined as a cognate (a unit that represents the information generated and stored in the cortex) in cognitive sciences.

The second one is memes that surface, stay, and diversify in the mezolymbic region, which houses the centers for reward and pleasure, fight or flight, and which generates simple and complex emotions.

The third type is memes that are associated with the back region of the brain that is in charge of activities pertaining to physical necessities, such as eating and drinking. Due to the make-up of our brains, personal memes for desire, fear, and other habits are significantly different from each other. But these three different types of memes play a role in shaping brain chemistry and culture. The way we think originates from these different memetic maps via different memes of subconscious content. Due to the differing makeup in personalities, because of memes and genes, people have different degrees of willpower. In summary, if there is not a problem regarding the foundation of genetic and memetic interaction, we develop and mature with the capacity to separate the good, right, and decent memes from the wrong, harmful, and disturbing ones. In this process, emotions and behaviors that are inside and outside of our will are subject to regulation and the control of psychological and spiritual states, and genetic-memetic systems. We should not forget that our ideas, emotions and behaviors are determined under the control of our intelligence, conscience, and willpower, which are the dynamics of our soul.

Basal ganglia subcircuits distinctively encode the parsing and concatenation of action sequences.
Jin et al. Nature Neuroscience, Jan 2014.

When we learn to play a musical instrument – say the guitar – first, we have to learn notes, scales and chords; only then we will be able to play a song. The very same rule applies to our basic functions. For example, when we learn how to read, we first learn the alphabet and the rules of grammar, and then we start making sense of sentences. Neuroscientists have been intrigued by this process for many years and they have wanted to understand how our brains efficiently perform complex cognitive functions by connecting separate elements to produce a unique meaningful sequence. A recent study shed some light on this very important question. Scientists found that a specific area of the brain, the basal ganglia, can signal the integration of individual elements into a behavioral sequence. Scientists designed an experiment where they first trained mice to perform gradually faster sequences of lever presses. This behavioral test is very similar to a person learning to play a guitar solo at an increasingly faster pace. Then, they recorded the neural activity in the basal ganglia of mice performing the task and discovered that basal ganglia neurons treat a whole sequence of actions as a single behavior. This mechanism is called “chunking,” which allows the brain to efficiently organize memories and actions by integrating individual sequences. It seems like the basal ganglia implement the “chunking.” The basal ganglia are known to include two major pathways, the direct and the indirect. Scientists found that these two pathways show similar activities during the initiation of movement, but show differential activations during the execution of behavioral sequences. Interestingly, basal ganglia circuits are implicated in Parkinson’s and Huntington’s disorders, in which learning of sequences are compromised. Further studies will reveal a more mechanistic understanding of sequence integration in the brain and potential interventions to enhance it in neurological disorders.

Single Gene Separates Queen from Workers

Ubx promotes corbicular development in Apis mellifera
Medved V. et al. Biology Letters, Jan 2014

In a hive of honey bees, the queen and worker bees have very different jobs. A new study shows that a single gene called Ultrbithrox (Ubx) separates a queen from worker bees. The Ubx gene was previously known to control leg and hindquarter development in bees. Interestingly, researchers now identified three functions for Ubx specific to worker bees. First, Ubx promotes the development of a smooth spot on the hind legs where the “pollen baskets” are located. Second, Ubx directs the formation of eleven perfectly spaced bristles on the section of the leg called the “pollen comb.” Third, Ubx mediates the formation of the “pollen press” which is a protrusion that helps pack and transport pollen back to the hive. Essentially, the Ubx gene promotes the development of three different physical structures on worker bees so that they can collect and transport pollen. Researchers confirmed these findings by silencing the Ubx gene genetically in worker bees and found that specialized leg features, including pollen combs and pollen presses, completely disappeared in the absence of the Ubx gene. Moreover, analyses of other bee species in the region revealed that the size and complexity of pollen baskets are directly correlated with the social behaviors of the particular bee species, suggesting that pollen baskets have yet-to-be-identified roles on the social behaviors of bees. Furthermore, the pollination of 35 percent of the world’s crops (with a $216 billion market value) depends on bees carrying pollen from one flower to another. This study might help us to develop new genetic approaches to make bees better, more efficient pollinators and to ultimately combat the worldwide pollination problem.

Molecular Switch in Aging Blood Cells Discovered

A canonical to non-canonical Wnt signaling switch in haematopoietic stem-cell ageing
Florian MC et al. Nature, October2013

Every single cell in our body ages over time. The aging of a cell is typically characterized by the progressive loss of physiological function and increased vulnerability to death. The aging of our cells/tissues/organs is the primary risk factor for any human diseases. One critical cell type that dramatically changes its properties during aging are blood stem cells, aka Hematopoietic Stem Cells (HSCs). Young HSCs have the capacity to differentiate into the diverse lineages of erythroid, lymphoid, and myeloid cells. Young HSCs are polarized (asymmetrical) cells, in which distinct cytoskeletal proteins (also called the “polarity complex”) are asymmetrically distributed within. However, the aged HSCs are mostly apolarized (symmetrical) cells and they differentiate only into lineages of myeloid cells (including, red blood cells, macrophages and monocytes) rather than lymphocytes (white blood cells in the immune system). The molecular changes in aging HSCs have largely been unknown. A recent study published in Nature shed some light onto the molecular identity of the ageing HSCs. Scientists showed that ageing HSCs have higher levels of a secreted protein called WNT5a, whereas the young HSCs have almost no WNT5a protein expressed in the cell. Moreover, the increased levels of WNT5a are found to attenuate the levels of the “polarity complex” proteins in HSCs and thus result in apolarized cells, which resemble the aging HSCs. Furthermore, transplantation studies revealed that increased WNT5a levels cause aging-related phenotypes and low Wnt5a levels promote a rejuvenation process in mice. These findings show that Wnt5a is the key molecule that controls the shift between young and old HSCs. Therapeutic approaches using antagonists of the Wnt5a molecule could potentially alleviate aging-related pathologies in the patients with a variety of blood diseases.

Harming our bodies or health is a betrayal against this incredible gift. One of the major ways people harm the body is through smoking cigarettes.

Smoking harms human health in countless ways. It is one of the main causes of many diseases, such as lung and throat cancer, along with cardiovascular and respiratory track diseases, such as chronic bronchitis. According to the latest report from the World Health Organization, smoking remains the fourth of the top ten risks that threaten human health. Approximately 20-30% of adult fatalities are caused by ailments contributed to by smoking. Recent studies have shown the negative effects smoking has on human reproductive functions.

Effects on fallopian tubes

Smoking has a negative impact on female reproductive organs; this impact is determined by how long, and how much, a woman smokes. It may cause infertility by damaging the fallopian tubes that serve as a ground for the egg to be fertilized by sperm. In many studies, the risk of damage to the fallopian tubes was very high – this danger increases if a woman starts smoking a pack a day before the age of 18.

Effects on female hormones

Many toxic substances in cigarette smoke, including nicotine, directly inhibits the activity of the enzyme called aromatase, which plays a major role in the synthesis of the female hormone (estrogen) in the ovaries. Depending on the biological function, estrogen can be found in three different forms: as estrone, estriol and estradiol. Polyaromatic hydrocarbons found in cigarette smoke stimulate the microsomal cytochrome P-450 enzyme system that degrades hormones in the liver and, consequentially, increases conversion of estradiol with high biologic activity into estriol with the lowest activity. Alkaloids, one of the harmful substances found in cigarette smoke, were discovered to prevent production of progesterone in the ovaries. This plays a role in preparing the womb and in continuation of the pregnancy during the first three months. Therefore, smoking leads to progesterone deficiency during the early stages of pregnancy, causing miscarriages.

Effects on the maturation of the egg

The concentrations of the FSH hormone that is involved in the maturation of reproductive cells in the ovaries are especially high in young female smokers. In other words, a resistance develops against the FSH hormone in the ovaries and higher FSH hormone levels are required for the maturation of the egg. Thus, fertilization problems and missed periods can occur because of an absent reproductive cell. During the treatment of such patients with insufficient egg cell maturation, there is a 50% decrease in the success of the implantation (placement of the fertilized egg into the womb) and the continuation of the pregnancy in smokers when compared to nonsmokers. This means smoking significantly reduces ovarian functions, and ovarian stimulation becomes inadequate at earlier ages in women.

The negative effects of smoking on the reproductive system are also observed during the implementation of reproduction methods such as in vitro fertilization and assisted fertility technologies. The presence of high androgenic hormone levels (pre-metabolites of gender related hormones: androstenedione, DHEAS and testosterone/SHBG) in female smokers has been found to decrease the possibility of pregnancy during in vitro fertilization efforts.

Effects during pregnancy

There are many harmful consequences of smoking during pregnancy, especially for older women who are pregnant. Some of these consequences are premature birth, miscarriage, retardation of development, inadequate baby weight, perinatal mortality, ectopic pregnancy, placental praevia, and placental abruption. Placental praevia is the abnormal placement of placenta in the womb. In this case, depending on the excessive bleeding that occurs after the eighth month of gestation, the lives of the mother and fetus become imperiled, and fetal development is hindered. Placental abruption occurs depending on the premature separation of placenta from the womb, causing excessive bleeding that can also endanger the lives of the mother and baby.

In pregnant smokers, the postnatal ratio of infant mortality and disability increases as a consequence of deficiencies involving lung function and nerve development. These effects are directly proportional to how much a woman smokes. There are also negative impacts when a pregnant woman is exposed to second hand smoke by a spouse or close friend. Harmful metabolites of nicotine reach the baby via the placenta. Furthermore, nicotine is degraded slowly in the liver of a pregnant woman. Inadequate baby weight is related to smoking dosage and time.

Due to smoking in the early stages of pregnancy, the hormone levels of estriol, estradiol, progesterone and hCG, hPL which is secreted from the placenta, have been found to decrease. This reduction, which is observed in parallel with the amount of smoking, can result in miscarriages.

Toxic polyaromatic hydrocarbons have been found to accumulate at elevated ratios in the wombs of women who were exposed to cigarette smoke for a long time. During pregnancy, this situation leads to the deterioration of sertoli cells located in the reproductive glands of male fetuses. These glands assist in sperm production during adulthood, and damage to them can therefore cause a reduction in sperm generation.

An insufficient placental development occurs because of the negative effects of nicotine, cadmiums, and polyaromatic hydrocarbons damage the reproduction of trophoblast cells that make up the placenta. This situation explains the increasing miscarriage ratios among female smokers.

The free T4/TSH ratio in the serum of the umbilical cord, which connects the fetus to the placenta, increases in the babies of smokers compared to those of nonsmokers. This means that in babies of smokers, the thyroid glands may become overactive during birth. Depending on a mother’s smoking habits, this hyperactivity of the fetal thyroid increases the metabolic speed and the amount of consumed oxygen in the body, thus leading to the inadequate development of fetus.

Menopause occurs two-to-four years earlier due in women who smoke, as compared to non-smokers. This is due to the aging of the eggs. The risk of entering menopause before the age of 45 in women who quit smoking at least ten years prior is 87% less than smokers who don’t quit. Therefore, the earlier a woman stops smoking, the lower the risk of early menopause.

Effects of smoking on men

In research studies, it has been discovered that smoking has many harmful effects on testicular development and functions. These effects can be summarized as follows:

• Reduction of semen volume and quality, increase in its adhesiveness, delay in its becoming liquid, and resulting deformation of the sperm.

• Reduction in the number and mobility of sperm cells.

• Delayed sperm nucleus maturation, deteriorated DNA integrity.

• Decrease in the production of testosterone from Leyding cells.

• Decrease in the egg fertilization capacity of the sperm.

As a consequence of these negative effects, male infertility can occur. As the amount of daily cigarette consumption increases, the number, strength, and types of anomalies also increase. In a study conducted in 2010, smoking has been showed to decrease zinc levels in the seminal plasma. As a result of this decrease, oxidative agents populate and DNA breaks take place, thus causing a disruption of sperm functions and infertility. Zinc deficiency at the same time leads to the destruction of seminiferous tubule cells where sperm cells are produced. Paternal smoking generates negative results during the application of assisted fertility methods (such as in vitro fertilization). The damage in the sperm DNA of the father can disrupt the embryo development. The risk of anomalies, cancer, and genetic diseases increases for the fetus.

Cigarette smoking clearly occupies a position as one of the worst enemies of mankind because of its destructive effects on the body. In this case, it does not make any sense to try finding excuses for smoking, for it is harmful to the body that has been loaned to us as a gift and a temporary property.

Cihanoglu is a professor of medicine in KATU, Trabzon, Turkey.

If we consider human nature as a book, the encoded information contained within, together with all the elements of inner and outer environments (bio-psycho-socio-cultural), becomes meaningful and functional. This is because each book has a visible structure composed of letters (semiotic DNA sequence) and a manifested meaning (semantic web) in a particular environment. From this point of view, genes should not be seen as mandatory codes, but should be considered as similar to the art of marbling (or ebru, which is the making of different patterns on a fluid by small vibrations of the ink droplets), for they are created by the united effect of various dynamic forces, and can only be understood accordingly. Human willpower and responsibility will also gain meaning and value when they are analyzed within the framework of the reaction intervals presented within the motifs of human nature which are shaped by the mutual effects genes and cultural factors have on each other. In this sense, human nature and culture should be evaluated together. We can organize the factors that determine human behavior and manners under three main titles – genetic, physicochemical environment, and psycho-socio-cultural factors. We can only speculate statistically as to how large or small a role each factor plays in development.

Behaviors like an inclination to crime, having intimate feelings for same sex individuals, cognitive and sensory sharpness, a desire for excitement and risk, or an inclination to addiction cannot be described by one or two genes. For instance, there are many factors (environment, genes) involved in acts of violence. However, one missing and insufficient factor can trigger violence. For instance, the Monoamine oxidase A enzyme is encoded by the MAO-A gene; this enzyme is in charge of degrading neurotransmitter molecules such as dopamine, serotonin, norepinephrine (these enable signaling between nerve cells). Depending on the mutations or polymorphisms of this gene, if the enzyme cannot function sufficiently, these individuals display an inclination towards violence and aggressive behavior. But if the person is aware of the situation and gets educational support from others, this behavior can be controlled.

Similarly, every person has a variable degree of genes that put them at risk for cancer. If these genes are activated via environmental factors – such as smoking, poor nutrition, mutagens, carcinogens – cancer may develop. On the other hand, if a person is lacking the cancer-causing genes or has low inclination towards cancer, such a person may not get cancer, even if he or she is a smoker. Similar statements can be made for genes associated with addictions, sexual perversions, and violent tendencies. More significantly, we can produce more value and meaning out of behavior-related genes when we evaluate them according to their context, position, and other factors, along with their relations to other genes. That is to say, there is a complicated network of factors that shape behavior. That’s why a DNA sequence alone cannot determine, all by itself, the development of emotions and manners, skills, and personality. In other words, phenotype can never be predicted 100% just by the interpretation of genetic information.

Brain and personality development is a multi-faceted, exposome mystery. From the start of pregnancy, especially throughout the preschool era, everything one is exposed to, and the way those events shape one’s nature, is called exposome. This can include subconscious events, for all sorts of personal history plays a role in such development. The connections of 1011 neuron cells that exist in an average human brain are not only determined by genes. Human DNA contains 6.2 x 109 nucleotide (letter), or information. Reading and using this raw information depends on many factors. Neurons can establish new connections via internal and external stimuli, while on the other hand, the number of neuron cells and connection networks can be changed by the neurochemical substances and hormones that they synthesize. All of the information required to define fine details in the motifs and connections of brain cells is not present in the genome. Mere environmental factors are not enough to complement this missing information.

Aside from these, many factors play a role in brain development and function. When the ends of axons and dendrites extend, they do so by recognizing nanomolecules that guide them all the way to the target organ or region. They happen to make minor changes and deviations during this extension. These changes are extreme enough that this extension is part deterministic and part trial and error. They reach the target through a statistically systemic algorithm but with a certainty less than 100%. Axons that are extended from eyes to the brain have a 1% possibility of taking a wrong turn at optic chiasm, and therefore not reaching the brain or arriving at the wrong region of it. However, there are also signalization systems built in our brains that recognize and correct these errors. If axons cannot receive the correct signals from target neurons, they get degraded. And sometimes a neuron of the axon terminates itself. These observations clearly show that brain development does not take place by a molecular program that is predetermined down to the minutest details but rather through a flexible program open to changes and errors.

This flexible program is explained by materialistic philosophy as “chance,” which basically means being in the right place at the right time to encounter the right factors. The same program, in religious literature, is explained by factors known as fate, kismet, destiny, divine blessing, and grant. Aside from that, there are also certain uncontrollable activations and a genetic background in the brain that are involved before we start a conscious action. From this perspective, motifs generated by biological and genetic inclinations set the infrastructure for the freedom of decision making and self-determination. Since our thoughts, emotions, and acts are formed within the neurogenetic and neurochemical construct of the brain, the motif that is created by the background here generates inclinations for specific acts and behaviors. In other words, events that take place in our brain chemistry during the fetal period and early childhood years are significant determinants of human development. The human brain can function in a state with willpower and consciousness, but can also function automatically, without consciousness. Briefly, it is through our genes that the framework of what we can achieve, our reaction intervals and threshold values are determined, and the possibility of an act is indicated. But the boundaries of the final decision are determined via statistical possibilities as a result of a person’s interaction with their environment. Therefore the boundary is not determined in a mandatory fashion, but via external dynamics (like manners, beliefs, or moral nourishment).

Human willpower is our capacity and strength to make free decisions and selections under the effects of spiritual, genetic, and environmental frameworks (endophenotype). The decisions and selections cannot take place independently from the sources nourishing one’s metaphysical world, cultural circles, or from the impact of neurochemicals in the brain and our hormones. “God burdens no soul except within its capacity” (2:286) is a sign of mercy and compassion from the Qur’an, indicating that the field of action and boundaries of the human willpower are determined based on multiple factors and wise causes. Producing customized religious rulings according to one’s natural strengths and weaknesses is also a very meaningful legal action in Islamic law. It is, in a sense, an acknowledgement that everyone has trials and experiences that are different than others’.

Humans have responsibilities within defined, limited conditions, and they can only make decisions within those permissible intervals of conditions and the constraints of their natural dispositions. If we can analyze human actions in a model that looks into their dispositions, cultural environments, genetic inclinations, and spiritual and moral nourishment, then we can attain better results in the education and character development of human beings.

Each factor mentioned above affects the child’s sexual separation and differentiation to various degrees. Misbehaviors during sexual development may emerge as a result of a complex mosaic of biological, psychological, sociocultural factors. There is not a complete consensus around the main reasons for this, yet each researcher favors one factor in the light of their expertise and ideological choices. However, objective observations and research point out that the quality of relationship between the parents and children is very influential in this matter. The display of unhealthy sexual inclinations stems from a negative background where there is not enough parent-child relationships to help the child develop. In families of children with strange sexual behaviors, a suppressive, excessively controlling model of mother and a distant, aggressive model of a father who resorts to violence are often found to exist. That is why many problems with intimacy and sex that occur later in life can be viewed as a developmental ailment and a problem of insufficient parental communication rather than a mandatory genetic phenomenon.

Various problems can arise when healthy differentiation and separation do not take place during a child’s development. A child, in the beginning, is like a part of the mother. If differentiated by detachment from the mother, and from her compassion and care, a child struggles to develop a healthy sense of ego. Such a child becomes inclined to develop a personality that is dependent, passive, and lacking sufficient confidence.

Research clearly states that each child is born with different inclinations and threshold values that are determined genetically and hormonally for each of his or her possible characters and behaviors. These potential inclinations and threshold values can surface depending on internal and external stimuli and educational styles. Even though both genders carry hormones belonging to each other naturally, during development one steps forward upon expression of encoded gender genes. When it comes to displaying sexual abnormalities, everybody is, genetically speaking, a dry log or a wet log. A dry log can easily catch fire, a wet one does not. However, it is the responsibility of society and parents to provide a spark-free environment for the dry log. Spiritual and biological nourishment during the developmental process are found to be significantly influential in diseases and aging, in disorders of character development, and in anomalies in sexual behaviors. When proper measures are taken timely, via suitable environments and educational modes, the possible surfacing of behavioral pathologies may be prevented or reduced for children potentially at risk. Through correct guidance and education, the expression and regulation of genes can be altered and managed, controlling these naturally present inclinations.

Cezmi Aydin is a freelance writer in natural sciences.

References

• Alper, Joseph S. (1998). “Genes, free will, and criminal responsibility.” Soc. Sci. Med. Vol. 46, No. 12, pp. 1599 1611
• Meyer, Lia Midori Nascimento, Gilberto Cafezeiro Bomfim, Charbel Nino El-Hani. 2011. “How to Understand the Gene in the Twenty-First Century?” Sci & Educ. DOI 10.1007/s11191-011-9390-z
• Levitt, Mairi and Neil Manson. 2007. “My Genes Made Me Do It? The Implications of Behavioural Genetics for Responsibility and Blame.” Health Care Anal. 15, pp. 33–40.
• Richardson, Brian. 2011. “What’s wrong with me? Coming to terms with same sex attraction.” Nursing Children 24 and Young People. October 2011. Volume 23. Number 8. pp. 22-24.
• William J. Jenkins. 2010. “Can Anyone Tell Me Why I’m Gay? What Research Suggests Regarding The Origins of Sexual Orientation.” North American Journal of Psychology, 2010, Vol. 12, No. 2. pp. 279-296.
• Botz-Bornstein, Thorsten. 2010. “Genes, memes, and the Chinese concept of wen: toward a nature/culture model of genetics.” Philosophy East & West Vol. 60, No. 2. April 2010. University of Hawaii Press, pp. 167–186.

What are complex systems?

If there are multiple elements (variables/factors) interacting with each other in the creation of an event or a being, this structure is called a “Complex System.” For example, in the air system, air and water molecules are a factor. Plants and animals in an ecosystem can also be considered as a factor. These are interconnected to one another in a way hard to imagine and have impacts on each other. Systems with these specifications display complex situations throughout time. For example in the medical field, a disease is described multi-factorial if many factors (causes) take part in its development. However in the past, these laws, specifications, and progress-dependent patterns of the multifactor diseases had to be overlooked due to the lack of a suitable paradigm to study with. But today, with the complex system paradigm, we have a greater access to the inner dynamics of these multi-factor diseases.

Multi-factor systems in terms of structure and function exhibit complex features during the process. Thus, complicated features of a complex system have been found to be dependent on the “Force Law” when investigated with the complex system paradigm. They also establish the basis for principles and laws that are occurring coincidentally. According to the Force Law, in all complex systems, small scale changes occur in greater numbers, and larger scale changes happen less often. This state corresponds to the same direct line, when plotted on the x-y plane logarithmically with scale of changes versus chances of events being created. This indeed results in the stability of the system in the macroscale and yet reveals the variability and instability of the microscale. In other words, the state of the macrosystem is put forth momentarily by selection among many micro incidents, which, for believers, is an indication of an ultimate Divine will in possession of infinite power. The information level, energy and interaction strength of such events or beings plays a great role in the possible selection of micro incidents in the grand scheme of causes.

Complex systems that become visible via space-time river also enters a dynamic cycle which is composed of sub-critical, critical, and super critical states. In this way, events and existence become subjected to newer manifestations or degrees of glory, as for believers, life and existence are artworks of God and His Divine attributes in the visible universe, which resembles a drawing board. Living things display an adaptive and dynamic character along with being a complex system. Healthy processes in the human body display adaptive dynamic complex system properties yet exhibit complex behaviors that bring system down like cancer as well. The medical world in recent years have been referring to cancer more so than before because of undetermined factors in its development, hardships encountered during diagnosis and treatment; as cancer is a multi-factored disease, it is necessary to look at cancer with the complexity lens.

The science of complex systems which studies multidimensional and multifactor relations states that in each complex system there are common features, and that these features can also be observed in cancer just like in all other scientific fields and in all scales. The following will focus on the subject since cancer makes a good metaphor in understanding complex systems of behavior.

In complex systems, a whole system means more than the total value of its factors. This principle emphasizes that properties of events and beings that are the sum of many separate factors do not exist in separate units or tend to disappearas each part is handled more individually. The deduction-reduction examples of a peacock coming out of an egg, a tree growing from a seed, and water that consists of various elements are used as metaphors to explain matters that pertain to belief and bear complex system properties. There are many genetic, epigenetic, metabolic, internal and external factors in ontogeny of cancer, however it only develops with the interaction of these elements and differentiates from regular cells. According to widely accepted views, in order for a cell to become cancerous, it is not enough for it to undergo many genetic mutations on its own. The few mutations that take place in a specific order alongside other epigenetic factors could lead to a tumor and cause a “system death” which means much more than the total value of components. That is why death occurs systematically in humans-cell death, tissue death, organ death, system death (excretion and transport) and death of organism.

All complex systems not only have a specific perimeter but they also remain a part of this boundary. This feature brings attention to the fact that there is even a relation between the Sun and and eye of a mosquito. Cancer starts out with a single cell made up of specific inner parameters, in a particular placement within a tissue. It is not possible for a cancerous cell to proliferate for a long time and cause the death of an individual all by itself. It can cause death as a result of communication with surrounding cells, conversion of these into cancerous types, and dispersion through blood vessels into other organs.

Inhibition or the delay of these stages makes up the most significant strategic approaches of the therapy. Because of this, while a cancerous cell is programmed to change its surrounding it also begins utilizing the nutrient sources of surrounding live cells for itself, as if trying to resolve an optimization problem, and causes disruption in the system by displacing other cells with an uncontrolled proliferation potential. This incident points out that there is no such thing as a “minor” in complex systems.

In complex systems, the more diversity exists within a system, the more powerful the system becomes. This principle brings attention to maintenance contingency and sustainability of the system and the conditions that pertain to it, for the lifespan of complex systems correlates directly with the abundance and diversity encompassed in it. This viewpoint could be observed in the case of a normal cell turning malignant. A mature tumor is a group of differentiated cell types that can provide interaction with neighboring cells through intra- and inter-cellular structures (matrix). That is why one of the characteristics of cancer is progress-dependent heterogenity at a cellular level. Because of this reason, although there is only one cancerous cell at the beginning, it can divide into different populations in time. Each population can be considered as an independent (sub-population) population since each has a specific genetic composition. This diversity is one of the major sources of problems in cancer treatment.

A continued relationship of factors with each other in a complex system has critical importance regarding system survival. Metastasis of a tumor not only depends on relations with surrounding cells but at the same time relies on the stimulation of blood vessel synthesis factors (angiogenesis). Two events are required for the dispersal of cancer cells freely; the first is the reduced interaction with other cancer cells. This can be possible with regulation of cell-to-cell connection molecules (adhesion). Second is the formation of new blood vessels via stimulation to connect with the bloodstream from the vicinity of the tumor. Finally, cancer cells that have reached their target of joining the blood stream should be able to leave the circulation, penetrate the new tissue, and manage to grow again. Metastasis is a situation for cancer cells to regulate limiting factors according to their new conditions to survive.

Behaviors in complex systems which display more features (emergent situation) that are not present in the units or even in the total value of constituents are plentiful and complicated, yet principles as causes behind these rich motifs are simple and determine the function of the system. Cancer disease arises from the execution of three simple basic principles of interaction, proliferation, and dispersion in cancerous cells. Interaction, proliferation, and dispersion do result in a healthy cell if it happens properly in the correct place, time, and dosage; otherwise it results in a cancerous cell. These three principles can cause cancer as a complex system disease or a healthy life which also displays characters of a complex system. Critical factors that control the management of these principles are location, position, timing, and dosage.

In complex systems, minor scale changes in initial conditions can lead to major effects after a certain amount of time, like a small snowball getting bigger as it rolls. Metaphorically, this situation is called the “butterfly effect” which assumes the possibility of a hurricane in one part of the world resulting from a complex chain of events starting with the strokes of a butterfly in another far corner of the world. Most of the adaptive complex systems are called “self-organized systems” in the scientific jargon, however these may exhibit such behaviors that are hard to overlook and believers would attribute to Divine guidance rather than to their so-called self-organization capacity. These systems organized with Divine guidance reach a “critical state” at the end. One of the models that were developed to explain this critical state is called the “sand pile model.” The system is named sub-critical when sand particles start to pile up on a surface, since at this stage the system is not affected from the fall of the next sand particle. As sand particles pile up, they reach a critical state in which every new particle added to the pile can lead to one of the following: 1. Nothing will happen; this is called the super-critical state. Particle can stay on top or roll down to the bottom of the pile. 2. Particles that hit the top of the pile affect other particles and can cause a small avalanche. 3. Sand pieces hit the top and cause some displacement of other particles. These displaced particles successively can cause a bigger avalanche.

This bigger avalanche again restores the system back into a sub-critical level. All complex systems arrive at these stations of sub-critical, critical, super-critical and again sub-critical successively in the flow of time. At each station they are dressed with a form of existence corresponding to a different macroscopic situation. So the outcome of the next situation is contingent on the mean average of microstates and thus points to a manipulator, who wills it to be that way. As a result, a minor event can lead to a “point of no return,” a stage called catastrophe, a super-critical state. These stages result in the continuum of the universe as it transforms and renews itself. A cancer cell also stops by the above mentioned stations and step by step, like a snowball turning into an avalanche, it can impact the whole body after reaching the super-critical stage, and lead to death. That is why early diagnosis (made during sub-critical or critical level) increases the chances of treatment, yet late diagnosis (at super-critical level) decreases therapy outcomes.

There is no hierarchical chain of command or control of causes on each other in complex systems. In other words, not only is there not a single factor in control of the system, but also a great number of factors function in a nonlinear mode of interaction. The development and progression of cancer as a complex system is controlled through interaction of internal and external factors, genetic, epigenetic, physical and metaphysical, tangible and intangible elements. Initial conditions that prepare the basis for cancer progress does exist in human genome, for genes that play a role whether in development, suppression, or regulation of cancer are built in the human genomic library from the beginning. Embryonic development is maintained with proper activation of these regulatory genes in the correct time and place during pregnancy. However, same genes may initiate cancer if not properly expressed in the right time, place, and level after birth. Moreover, all the factors that the zygote is left exposed to during its interaction with the surroundings leave a mark (memory) on the system. This is called “system exposition.”

Exposition forms microstates that will lead to positive/negative development of the organism through interaction with genetic and epigenetic memory of the system. That is why programmed cell death is put in place to eliminate damaged and dysfunctional cells that form in the system.

Cancer, as a consequence of progress-dependent corresponding interaction of genome and system exposition, is a system that can display chaotic behavior. Because of this, spiritual factors as well as physical ones may cause a “butterfly effect” in development of cancer and there is no single center of command that is designed to control each of these in the causation chain. This being the case, one cannot help but wonder how causes can comply with the force law of all complex systems and that they share common features without a hierarchical command on each other.

Each complex system is composed of holographic sub-systems. The human body is an ecosystem of various systems placed within each other. The well-being of the ecosystem depends on proper interaction and health of these sub-systems. A tumor can be considered as a local ecosystem (sub-system) where various species and clones exist in a human ecosystem. While each tumor grows, there are living and dead clone populations in it. One billion elements exist in a tumor as small as 1 cm3 (1 gr). If we omit cell death, this corresponds to the 35th generation of an abnormal cell. Ten more generations later this reaches one trillion cells. This way, a population that started out with a single cell exceeds the total number of humans ever lived throughout history. So, human death with cancer starts with the disruption of one single cell. Once reached a super critical stage, system death occurs when the cancer branches out via blood circulation and disperses into various organs, leading to disconnection between them.

Cancerous cell reminds us that there are no minor events in the universe and points out that the health of our social and spiritual world takes shape according to the rules of complex systems. As a side thought, we may easily infer from cancer that underestimating any seemingly minor misbehavior or a sin and failure of immediate action to make up for it may lead to undesired consequences in our social and spiritual lives. It is also significant to be aware that we do not have an absolute control over our future and we cannot determine whether we will attain healing or not; however we can and we should try with science to elucidate some of the tangible causes of the disease and can point out some possible ways of treatment.