It is uncommon that we observe the background details of a well-produced film or notice the subtle masterpieces behind a state-of-the-art play. Aside from those that are very observant, these elements usually only come into view when production experiences a horrible mishap, perhaps if an actor’s costume is ruined or they forget their lines. The same can be said for the quiet mechanisms and systems, which our lives are dependent on, on a daily basis, namely our organs and their exceptionally complex makeup that we often take for granted. This issue aims to take a deep look at some of the processes that affect us every day that we usually do not think about.

Modern medicine is perhaps one of the greatest blessings of our time, as synthetic drugs are able to cure complex diseases in previously unknown ways. These medicines undergo intense research, testing, and scrutiny before being released to the general public. We quickly rush to the doctor’s office and pop a few pills when we feel ill, yet we rarely ponder over highly exhausting and costly process of developing these drugs.

Our hearts never rest from the moment we are born to the day we die. This organ we don’t usually think about pumps onwards multiple times per minute and allows us to perform our daily functions. In her piece in this issue, Ceyda Sablak reminds us how delicate the anatomy of this organ is and why we should maintain a healthy, balanced life of physical and spiritual activity, as many spiritual masters have seen a connection between our biological heart and our spiritual well-being.

Stem cell research has been a common point of discussion, debate, and controversy in the past few decades. Researchers argue that they possess an almost endless number of possibilities while advocates argue that they are derived in an unethical manner. The science behind them is fascinating, and the potential that they possess is undoubtedly inspiring.

Lastly, it turns out that our tears are integral to keeping our eyes healthy and itch-free. A lack of tears can result in a multitude of annoying and harmful disorders that can severely affect a person’s life. Searches have been underway to find the perfect “alternative tear” for those that suffer from tear related disorders. Who would have thought that something so simple contributes so much to our normal happiness and peace?

To attain happiness and to avoid mood disorders, which should we pursue

The messages of modern society are all too familiar to us: buy more, eat more, sleep more, take more pictures, and care less about the effects of our actions. We are encouraged to maximize pleasure while avoiding anything that inconveniences us. We cloister ourselves with our material goods and social media habits, promoting self-centeredness. This induces a fluctuating happiness in which phases of pleasure and displeasure repeatedly alternate, which can result in various mood disorders and has been linked to decreases in well-being. In this article, we are going to analyze self-centeredness and its consequences and also interpret its role in a variety of mood disorders and various areas of life.

The Self-centeredness / Selflessness Happiness Model (SSHM) is a theoretical model proposed by Dambrun et al. in 2011 [1]. This model represents different sorts of happiness that are dependent upon the self, particularly the structure of the self. They claim that self-centered psychological functioning derives from how someone perceives themselves and the belief that they are powerful, permanent, and independent. This functioning causes fluctuating happiness and afflictive affects which are also the roots of many mood disturbances. This is heavily contrasted by the perception of the self as flexible which leads to selfless psychological functioning and is a crucial factor at attaining more authentic/durable happiness [1].

After proposing this model, Michael Dambrun conducted a study in 2017 that built upon this model. According to this research, self-centered psychological functioning allows individuals to fluctuate between joy and sorrow, a vacillation that results in afflictive affects. Conversely, selfless psychological functioning gives the individual more emotional stability and feeling of harmony with the environment. They tested these hypotheses in two studies consisting of a heterogeneous sample of citizens (n=547). Analyses of these two studies indicate that self-centeredness (measured by egocentrism and materialism) and selflessness (measured by transcendence and connectedness to others) were two different psychological constructs rather than strict oppositional ideas.

In addition to showing the distinct functioning, these analyses also revealed that self-centered functioning is significantly associated with fluctuating happiness that is the root of afflictive affects. However, selflessness is linked to authentic/durable happiness, which is the result of perceiving the self as flexible and harmonious with the environment and universe. These associations are mediated by distinct psychological processes. For self-centeredness, afflictive affects play a crucial role in the correlation with fluctuating happiness in self-centered individuals.

In contrast, selfless individuals attain authentic-durable happiness that is partially mediated by emotional stability and perceiving themselves as harmonious with others and the universe (2). In our view, individuals who are more concerned about their happiness are more susceptible to mood fluctuations and disorders, while individuals who have more significant interest for the happiness of others attain more robust and durable emotions.

These studies also suggest that self-centeredness causes problems in society; as such, we will to analyze the results later.

Fluctuating happiness in the self-centered individual

The idea of the self as a real, permanent entity with its distinct boundaries results in self-centered psychological functioning. Laborit’s [3] study suggests that each organized structure in the form of an entity seeks gratifications that positively reinforce it and avoids things that risk its homeostasis. The hedonic principal is a major ruler in self-centered functioning and is deeply associated with egoism, egocentrism, an exaggerated importance given to the self, and ego inflation (through material possessions, for example) (e.g. Higgins,1997) [4].

The hedonic principle and its associations are also correlated with some personality disorders, particularly narcissistic personality disorder [5]. This principle induces the individual to focus on attaining pleasure and avoiding displeasure. Feelings of temporary happiness, joy, and gratification are the result of impulsive actions for attaining pleasure and avoiding displeasure. However, only the presence or absence of certain stimuli reinforce the individual and only give temporary pleasure and happiness (Wallace & Shapiro, 2006 [6]). The experience of pleasure depends on circumstances, is an unstable condition that may soon become neutral or may be displaced with displeasure. (i.e., hedonic adaptation, e.g., Brickman, Coates & Janoff-Bulman, 1978; Lyubomirsky, 2011 [7]). Focusing on attaining more pleasure and avoiding displeasure lead an individual to recognize and realize the impossibility of attaining valued objects, durable pleasure, and cause them to repeatedly vacillate between pleasure and displeasure and the arising affects such as frustration, nervousness, anger, hostility, or jealousy, all of which damage their well-being and health (e.g., Miller) [8]. Contrarily, altruism, also called selflessness or focusing on others’ happiness, is significantly associated with a higher quality of well-being, health, and longevity [9].

Self-centeredness cause depressive symptomatology

A self-centered lifestyle may cause not only mood disorders but also social problems that also increase the prevalence of different mood disorders. Loneliness is a big problem in contemporary society, though we mostly live in crowded cities adorned with skyscrapers. As the title describes, a study conducted in 2017 shows loneliness and self-centeredness have a reciprocal effect that cause depression and various mood disorders, as well as health and social problems [10].

Loneliness increases not only the motivation to repair or replace deficient social relationships, but also the implicit motivation for self-preservation. John T. Cacioppo et al. reported a cross-lagged analysis of 10 waves of longitudinal data (n=229) on loneliness and self-centeredness (as gauged by Feeney and Collins’s measure of choric self-focus) in a representative sample of middle-aged and other adults. Loneliness increases the implicit motivation for self-preservation, and loneliness in the current year anticipates self-centeredness in the following year beyond what is reasoned by current-year demographic variables, self-centeredness, depressive symptomatology, and overall negative mood and emotions. Their study also revealed that self-centeredness in the current year foretells loneliness in the subsequent year, a reciprocal relationship that could potentially contribute to the maintenance of loneliness [12].

Generation Me and its consequences on human mood

An increase in narcissism with some indicators of increased self-focus in Americans born after 1970 leads authors to describe that generation as “Generation Me” [5, 12]. This narcissism and self-focus are also intimately related to self-centered psychological functioning since both are formed by an exaggerated importance given to the self, ego-inflation, and so on. We think self-centered psychological functioning may also be considered as a part of this dynamic, thus being a member of Generation Me may be one of the major risk factors for narcissistic personality traits and disorder [2, 12].

Narcissistic personality disorder (NPD) is a personality disorder in which there is a long-term pattern of abnormal behavior characterized by a grandiose self-view, unrealistic sense of entitlement, exaggerated feelings of self-importance, and a lack of understanding of others’ feelings [13, 14]. Narcissists who consider themselves to be superior to others, and also have unrealistic expectations for the future, become angry and aggressive when in trouble, take more resources for themselves and leave less for others, and value money, fame, and image over family, helping others, and community. Though narcissism has some benefits, like public speaking, it has lots of adverse effects on human mood and behavior and comorbidities with psychological disorders [15].

Selfless functioning

The principle of “harmony” has a primary role in the selflessly functioning individual; harmony directs all mental activities (conation, motivation, attention, emotion, cognition, behavior). Harmony and emotional stability are associated with empathy, benevolence, compassion, and deep respect; all of these have a beneficial effect on behavior and a reduction of psychological distress [2]. Many studies have revealed the results of altruism on happiness and health and have consistently found a deep and intimate connection between altruism and current and future health and well-being.

References

1. Dambrun, M., & Ricard, M. (2011). Self-centeredness and selflessness: A theory of self-based psychological functioning and its consequences for happiness. Review of General Psychology, 15 (2), 138-157.
2. Dambrun M. Self-centeredness and selflessness: happiness correlates and mediating psychological processes. Hung T-M, ed. PeerJ. 2017; 5:e3306. doi:10.7717/peerj.3306.
3. Laborit (1979) Laborit H. L’inhibition de l’action: biologie, physiologie, psychologie, sociologie. Edition Masson; Paris: 1979.
4. Higgins (1997) Higgins ET. Beyond pleasure and pain. American Psychologist. 1997; 52:1280–1300. doi: 10.1037/0003-066X.52.12.1280. [PubMed] [Cross Ref]
5. Jean M. Twenge The Evidence for Generation Me and Against Generation We Vol 1, Issue 1, pp. 11 – 16,First published date: March-01-20131177/2167696812466548
6. Wallace & Shapiro (2006) Wallace BA, Shapiro SL. Mental balance and well-being: building bridges between Buddhism and Western psychology. American Psychologist. 2006;61:690–701. doi: 10.1037/0003-066X.61.7.690. [PubMed] [Cross Ref]
7. Brickman P., Coates D., Janoff-Bulman R. (1978). Lottery winners and accident victims: is happiness relative? J. Pers. Soc. Psychol. 36, 917–92710.1037/0022-3514.36.8.917 [PubMed] [Cross Ref]
8. Miller et al. (1996) Miller TQ, Smith TW, Turner CW, Guijarro ML, Hallet AJ. A meta-analytic review of research on hostility and physical health. Psychological Bulletin. 1996;119:322–348. doi: 10.1037/0033-2909.119.2.322. [PubMed] [Cross Ref]
9. “altruism (n .)”.Online Etymology Dictionary. Douglas Harper. Retrieved 19 September 2014.
10. Cacioppo JT, Chen HY, Cacioppo S. Reciprocal Influences Between Loneliness and Self-Centeredness: A Cross-Lagged Panel Analysis in a Population-Based Sample of African American, Hispanic, and Caucasian Adults. Pers Soc Psychol Bull.2017 Aug;43(8):1125-1135. doi: 10.1177/0146167217705120. Epub 2017 Jun 13.
11. Twenge JM. Generation Me: Why today’s young Americans are more confident, assertive, entitled—And more miserable than ever before. New York: Free Press; 2006.
12. PubMed Caligor, E; Levy, KN; Yeomans, FE (May 2015). “Narcissistic personality disorder: diagnostic and clinical challenges.”. The American Journal of Psychiatry. 172 (5): 415–22. PMID25930131. doi:1176/appi.ajp.2014.14060723
13. Diagnostic and statistical manual of mental disorders: DSM-5(5th ed.). Washington [etc.]: American Psychiatric Publishing. 2013. pp. 645, 669–72.
14. Cai H, Shi Y, Fang X, Luo YLL. Narcissism predicts impulsive buying: phenotypic and genetic evidence. Frontiers in Psychology. 2015;6:881. doi:10.3389/fpsyg.2015.00881.
15. Diagnostic and statistical manual of mental disorders: DSM-5(5th ed.). Washington [etc.]: American Psychiatric Publishing. 2013. pp. 645, 669–72.

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

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

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

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

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

Mass trauma

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

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

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

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

Post-Traumatic Stress Disorder

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

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

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

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

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

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

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

Protective factors that may mitigate negative effects include:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Treatment for mass trauma:

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

1. Community level:

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

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

2. Individual level

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

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

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

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

References

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

Every essential oil gets its uniqueness not just due to one of its components but because of its delicate and complex admixture. The individual perfume and therapeutic value of each essential oil depends on this balance.

What is aromatherapy?

Aromatherapy is the practice of using essential oils, also known as volatile plant oils, for physical and psychological health. These essential oils and/or essences are concentrated liquids that are extracted from many different types of wild or cultivated plants. Essential oils can be obtained from different parts of the plant, such as the flower, leaves, fruits, bark, roots, and resins. Some examples of essentials oils are Agar oil, highly coveted for its wonderful fragrance, and Geranium oil, used in herbal medicine. As for essences, they can be obtained not only from flowers and resins but also from chemicals such as benzoins, and plants such as gaiacs and pines. Some examples of resins that can be used for their essences are Asafoetida, which is dried latex that certain Ferula plants exude from their tap root, and Myrrh, which comes from thorny plants of the genus Commiphora.

A brief history of aromatherapy

It’s hard to say when people first started using aromatherapy, partly because the practice of using plant-derived ingredients for medicinal (and other) purposes is as old as time. There is evidence that the Chinese may have used aromatherapy several thousands of years ago, with an emphasis on maintaining harmony and equilibrium. Some years after this the Egyptians were able to develop a machine that could distill cedar wood oil. Later on, the Greeks adapted aromatherapy from the Egyptians. “Istenshaque,” a form of aromatherapy, was first practiced in the Greek system of medicine by Hippocrates (460-370 BC). In the 11^th century, the renowned Avicenna developed a coiled cooling pipe that made the essential oil distillation process much faster. The term “aromatherapy” was eventually coined by the French chemist and scholar Dr. Rene Maurice Gattefoss’e (1881-1950) in 1930 and thereafter practiced as a medical science for the treatment of various diseases.

What are essential oils composed of?

From a chemical analysis standpoint and by chromatography it is evident that essential oils are not single entities but can instead be classified as compounds. Additionally, essential oils are volatile in steam, which means they will turn into a gas in the presence of steam. They differ entirely in both chemical and physical properties from fixed oils, which are also known as non-volatile oils. Animal or vegetable oils are very common types of fixed oils. Essential oils consist of many organic constituents which unite in a delicate and complex balance to produce a wide range of therapeutic and olfactory qualities. For example, the oil of the eucalyptus leaf contains no less than 250 different constituents. In one study, researchers were able to identify 40 different compounds in tea tree oil using chromatography methods (Journal of Agriculture and Food Chemistry). Every essential oil gets its uniqueness not just due to one of its components but because of its delicate and complex admixture. The individual perfume and therapeutic value of each essential oil depends on this balance.

Scope & methods

• Olfaction (shamoom): Aromatic medicines either in dried or liquid forms are kept in a vessel and the fumes are inhaled. Rose oil is often used in this manner.
• Inhalation (lakhlakha): Aromatic medicines or pungent medicines either dried or liquid forms are kept in a wide mouthed bottle and then inhaled. With this method the vapors of the medicines not only reach up to the nose but can reach down in to the respiratory passage as well. Camphor is a common choice for inhalation therapy.
• Massage (dalak): Some treatments involve massaging the oil into the skin directly, and can be one of the more effective treatment methods.
• Poultices: Essential oils used in poultices bring out impurities of the skin. These treatments sooth irritation and relieve congestion and pain. Most frequently, poultices are made up of linseed (Alsi) or mustard. These are particularly useful for chest complaints and skin diseases.
• Compresses: Used externally, particularly on eyes. They can be either hot or cold depending on the effect required.

Base oils and carrier oils

Most essential oils are not used in their pure, undiluted sate. Rather, they are mixed into a fixed plant oil base, like almond, soya, or wheat germ. These base or carrier oils act as balancing and stabilizing agents. They are typically pure, have little to no smell, and are easy for essential oils to dissolve in. The ratio of essential oils to base oils differs for each oil. For example, 2 to 3 drops of essential oil to 5 ml of base oil can be used for the body, and 1 drop essential oil to 5 ml base oil can be used for the face.

Some commonly used oils

• Almond oil: Oil extracted from bitter and sweet almond.
  Constituents: Olein is the chief constituent. Other constituents are glyceride and linoleic acid.
  Action: Skin softening agent, lubricant, nourishing and revitalizing.
  Uses: Wonderful for dry, wrinkled hands. Very beneficial for eczema and skin irritation of any kind.
• Castor oil:
  Constituents: Major constituents are palmatic, fatty acids, ricinoleic acid and glycerine.
  Uses: as soothing agent for skin rashes, in embalming, eczema, dryness of the skin.
• Soya oil:
  Constituents: Oleic, linoleic, stearic and palmitic acid.
  Action: Lowers cholesterol levels.
  Uses: To be taken every day in salad dressing or with rice dishes.
• Sage leaf (Salvia officinalis)
  Action: Antiseptic, astringent.
  Uses: Mouth washes and gargle, Alzheimer’s disease, memory loss.
• Thyme & thyme oil (Thymus vulgaris)
  Action: Antiseptic, anti-tussive, expectorant, spasmolytic.
  Uses: Cough cold, spasmodic pain.
• Lavender oil (Lavendula angustifolia)
  Action: Masks disagreeable odors, heals skin burn and acts as relaxant in premenstrual tension.
  Uses: In ointment, rheumatic pain.
• Aniseed (Pimpinella anisum)
  Action: Carminative, appetizer, hepto-tonic, stomachic, diuretic, emmenogogue, galactogogue, analgesic.
  Uses: flatulence, loss of appetite, liver disorders, indigestion, renal disorders, to stimulate lactation, for pain.
• Fennel (Foeniculum vulgare)
  Action: Carminative, stomachic, diuretic, emmenogogue & galactogogue and vermicide.
  Uses: flatulence, loss of appetite, indigestion, renal disorders, to stimulate lactation and worm infestation.
• Cumin (Cumin cyminum)
  Action: General tonic, digestive, antiseptic, bactericide, carminative, detergent (Jaali)
  Uses:Indigestion, loss of appetite, infections, flatulence, skin disorders.
• Cinnamon oil (Cinnamomum zeylanicum)
  Action: Rubefacient, carminative, powerful germicide, anti-rheumatic, digestive, analgesic, detergent.
  Uses: Skin disorders, flatulence, infection, arthritis and indigestion.
• Camphor (Cinnamomum camphora)
  Action: externally: rubefacient, internally-mild antiseptic, carminative, antipyretic.
  Uses: skin disorders, infections, flatulence and fever.
• Caraway (Carum carvi)
  Action: Carminative, antispasmodic, galactogogauge and emmenogogue.
  Uses: Flatulance, colic, stimulate lactation and dysmenorrhea.
• Myrrh (Commiphora)
  Action: Antiseptic, antibiotic, stomachic, emmenogogue, diuretic, anti-inflammatory, wound healing properties.
  Uses: as an essence and in perfumes, mouth wash, in anti-ulcer treatment and is cytoprotective.
• Clove oil (Eugenia caryophyllus)
  Action: Stimulant, antiseptic, stomachic, expectorant, sedative, carminative, antispasmodic, digestive.
  Uses: Mouth and tooth infection, flatulence, rheumatic pain, bronchitis, cold.
• Eucalyptus oil (Eucalyptus globus)
  Action: Decongestant.
  Uses: Internally: Mixtures, inhalations, lozenges. Externally: In ointments and liniments.
• Chamomile (Matricaria chamomilla)
  Action: Antiseptic, anxiolytic, digestive, disinfectant, carminative antipyretic.
  Uses: Insomnia, headache, migraine, facial neuralgia, sinusitis, dermatitis, acne, eczema, abscesses, boils, amenorrhea, pre-menstrual tension, cystitis, colic, loss of appetite.
• Sandal wood (Santalum album)
  Action: Calming action on dry skin, aphrodisiac.
  Uses: For dry and chapped skin.
• Rose oil (Rosa domascena)
  Action: Cardio tonic, resolvent, anti-inflammatory.
  Uses: In perfumery, palpitation, inflammation.

Precautions while using essential oils

Although essential oils are useful for treating a number of ailments you should still take the necessary precautions before using them. For example, you should always perform a skin test before using an essential oil, since everyone is unique and reacts differently to different oils. Body size, age, and sex also makes a difference. As for storage, essential oils should always be stored in dark glass bottles away from sunlight.

In our era that is characterized by stressful environments and ever-changing life styles, essential oil aromatherapy offers an optimal answer to the emerging health burden of degenerative diseases. It not only offers therapeutic but also preventative and restorative health benefits, without most of the side effects of modern treatment schedules. Hence aromatherapy with its wide scope and application potential offers a therapeutic solution for not only diseased body systems but also soothes the soul and the spirit, thereby taking care of the stress component that is prominent in many illnesses.

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

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

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

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

Initial studies

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

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

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

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

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

Just in time and in the right amount

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

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

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

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

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

Miraculous differentiation

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

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

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

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

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

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

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

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

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

Matter&Beyond: What was your motivation for writing the book, The Heart-Mind Connection?

Well, that book was a collaboration with Dr. Ting who is a Cardiovascular Surgeon and it was actually his idea. He’s a very enlightened surgeon in that he, over the years of training in a practice as a cardiac surgeon, came to realize that the experience of undergoing cardiac surgery certainly taxed the mind and that the interaction of mind and heart was extremely important for outcomes. If you’re a cardiac surgeon and your goal is to improve your patients’ lives it became very clear to Dr. Ting that in order for that to happen cardiac surgeons and cardiologists had to be mindful of the fact that patients needed to be emotionally and cognitively intact, and so he asked me to collaborate on this book, and the book focused on the interaction between mood states and cardiac states.

M&B: What is the nature of this interaction? Does the heart affect the mind or does the mind affect the heart?

It’s bidirectional. There is an interaction or there is a relationship between mood disorders such as depression, anxiety, anger, and hostility and the actual human heart. The connection between those mood disorders and cardiac function is extremely important. But then also if you go into the experience of having heart disease and you were fortunate enough not to have one of those mood disorders, the experience of having cardiac disease will put you at risk for developing mood disorders. So it’s bidirectional. You can start out with heart disease and wind up having your health complicated by mood problems, or you can start out with mood problems and have your health complicated by heart disease. There’s an unholy alliance between depression and anxiety on the one hand and heart disease on the other.

M&B: What happens, let’s say, if you are someone who has a history of a major depressive disorder? What happens to his or her heart?

Major depressive disorder is a condition characterized by certain clear-cut symptoms, and those symptoms include having a depressed mood everyday most of the day for two weeks or more that includes losing pleasure in life, something we call anhedonia, not being able to take pleasure in normal activities that would normally make you happy. Along with that is loss of interest in things, guilt, or feelings of hopelessness, helplessness and worthlessness, loss of energy, loss of concentration, loss of appetite, sometimes even leading to weight loss, not being able to move the way you’re used to. So it’s sometimes you just curl up in bed and this is something we call psychomotor retardation or withdrawal. On the other hand sometimes depression makes you agitated so you can’t sit still and you’re running around sort of ringing your hands and so on. And then the final symptom of major depression is suicidality or morbid thinking. Always focused on death or wanting to die. So that’s the common sort of a cluster of symptoms we see in major depression. Now, say you have no history of heart disease but you suffer from major depressive disorder. You increase your risk of developing heart disease by having this condition of depression. So your risk of having a heart attack for example goes up like 1-1/2 to 2 times what it would be in someone without depression.

M&B: Is it similar with anger and hostility?

Some people believe that if you’re an angry person or a hostile person, that also increases your risk of developing depression. Say you have depression and you unfortunately have a heart attack. If you remain depressed then your risk of having another cardiac event, another minor cardiac infarction or a cardiac arrhythmia would go up three and a half times what it would be if you weren’t depressed. So that means that this connection between the brain and the heart, between depression and cardiac disease are tremendously important in terms of public health. Because those two diseases are causing most of the disability that exists, by the year 2020, the World Health Organization predicts that heart disease will be number one and depression will be number two in the entire world. That includes the developed world, the industrialized countries as well as the developing low income countries around the world. So in terms of the book that we did we thought it was important because these two illnesses, first of all feed off each other and cause a lot of heartache in the population but they also are the most important diseases in public health.

M&B: The heartbeat change is associated with love or certain joy. What is the physiology behind that?

Let me preface it by saying that this is the age old philosophical question which Plato and Aristotle sort of debated. Love is an idea as Plato thought. So, is there sort of an idea of beauty and of love that exists outside of the materialistic world? Are we somehow plugging into that ideal world of love as material organisms? Or does it come as a result, as an epiphenomenon of the material world we’re living? Does it emerge from the biological material world that we’re living? That in a way becomes a philosophical question. As scientists when we see human behavior, there’s something that we do, and it’s called reverse engineering. Let’s look at the behavior or the experience of human love. Where does that come from? Let’s work backwards from human love to try to understand in a biological way where it came from. We are the ultimate mammalian life. We might start a little controversy about that and especially with the all wars that we fight, but be that as it may, we are these high level, high functioning mammals. Our infants are born [in need of] altruism, which means that they are absolutely helpless when they are born. So parenting for the human being is extraordinarily important for the continuity of our species, and so our infants are in total need of care.

M&B: Isn’t this the same for all the animals?

It’s different in reptiles. If you go to Borneo and you study the life of the Komodo dragon, you’ll find out that komodo pups know immediately what they have to do when they plop out of komodo mommy. They have to roll around in their own feces in order to throw mommy off the scent because mommy will look at them as food. So that’s their strategy for avoiding being eaten by mommy. They also know how to climb up trees to get away from mommy. So here the survival strategy of reptiles is not one of attachment; it’s one of separation. All psychiatry is tied up in that simple fact. There would be no psychiatry if we were reptiles. But because we’re mammals, there’s psychiatry because all of the disorders we have are really disorders of a dysfunction in parental and social attachment. Only mammals for example have a part of the brain called the paralimbic cortex. So reptiles have primitive limbic areas, they have hippocampus, they have amygdala, so they show fear, and they act when they’re threatened, etc. They’re outfitted with those structures which allow them to do those simple attachments-attachments to food and to sexual objects etc., but don’t allow them to do social attachments very well, and there’s some reptiles that are better at it than others. Crocodiles, for example. They do a version of taking care of their pups. Birds also take care of their nestlings very well, and crocodiles actually have brains that are more kind of on the bird-like end of the spectrum, allowing them to do a better job as reptiles taking care of their young and having something of a social life. Nothing to the extent that mammals do and you can look at a mammal brain, and you can see where this is taking place. So the anterior cingulate is an area of extreme importance for mammalian behavior.

M&B: This unique mammal feature, the limbic system and the paralimbic system; would you elaborate a little bit more on them?

I had the privilege of meeting back in 1990 Paul McClain, who is a famous neuroscientist who coined the term limbic system. He studied emotional parts of the brain in reptiles and in monkeys and in human beings. He talked about what he called the mammalian behavioral triad. There are three things that mammals do that reptiles don’t do very well. One is that all mammalian infants cry for their mothers in the same way, so every lamb baas for its mother the same way. Every human infant cries for its mother in the same way, that’s called a separation cry, and you can study it. So when you look at rats they have an ultrasonic isolation cry; you can study it, and you can deprive them of relationships and you’ll see the cry. That’s typically mammalian. Another feature is play, so mammals play, and that serves a social binding function. We play sports together; it serves a social binding function. Then the third thing is maternal nurturance which is extremely important, and mammals do that parental nurturance piece pretty well.

M&B: Are there any experiments that may illustrate the role of love?

There are a couple of experiments that Paul did and they are very illustrative. They get us back to a focus on love. So one experiment was to take hamsters and you can ablate, sort of take out the anterior cingulate. When you do, the hamster pup no longer cries for its mother when it’s separated and the hamster mother no longer responds when the hamster pup cries for her. You can also put morphine in that area, and get pretty much the same results. So you could put morphine in the hamster pup’s brain in the anterior cingulated, and the hamster pup will no longer cry for their mother, it distorts that bonding. And you can do that with squirrel monkeys too and you’ll get similar results.

M&B: Do the results apply to human beings as well? Could the use of morphine stop a healthy heart or brain from giving love or responding to love?

One of the real problems that we face in psychiatry is when we run across an addicted mother. What happens to the mother child relationship when the mother is addicted to heroin or to cocaine or to other drugs of abuse? The child gets neglected, the mother no longer responds to the needs of the child. So we see there’s even a reflection of those basic experiments in the human model when we’re talking about maternal-child relationships. So again that’s kind of circumstantial evidence where there’s reverse engineering, and mothers also have this phenomenal hormone, neuropeptide hormone, this again is exclusively mammalian, called oxytocin. So it’s used in pregnant women to get them ready to give birth, and so once a pregnant woman gives birth it’s responsible for milk production and so on. This is another example of this – if we think about maternal love, one of the requirements for maternal love is that there needs to be oxytocin involved. Oxytocin needs to allow that brain to have the experience of being connected and bonded to offspring.

M&B: The relation between the brain and the other organs such as the heart, is it really a top down relation where the brain commands, or is it a bottom-up relation where bodily sensors form the human brain?

What you’re referring to when you bring up this fact that the body sends markers up to the brain, and the brain takes note of that and becomes behaviorally engaged, that is absolutely true, and it’s something that Tony Damasio calls a somatic marker hypothesis of how the brain works. This is also something that William James postulated in the late 1800s-that emotion is a reflection of the body’s activity. Your heart racing or your stomach turning, emotion is secondary, it’s the brain trying to make sense of what the body is going through. What came first, the chicken or the egg, that kind of a problem. The fact is, the organism works as a unity and you need all of its component parts for it to work, and you really can’t tease a part, what came first and what came second.

M&B: From our physiology, it is evident that we are born to love.

It is very spiritual about this kind of understanding of love and connecting it back to the brain. How the heart becomes a reflection of what the brain is about, and also this need we have as human beings for connection. Spirituality really is this need we seem to have as human beings to be connected to something greater than ourselves. So we have this part of our brain, the prefrontal cortex, which allows us to think into the future and when we think into the future, we gain security when we see a future of connectivity, of attachment. That becomes a workable definition of spirituality. So many of us feel connected to a higher power, to God or to nature, but that is also a common reflection of what people refer to as love, and again you can choose to understand its biological origins. The body will be connected up with that whole experience, so your heart will be connected up. If you’re feeling connected to God, or to the scene of an ocean, and you’re feeling connected to the universe, when you’re looking up at the stars, there will be a bodily sensation connected up with that experience, and that will become for you part of what you understand to be spirituality.

Almost all of us are familiar with the fact that our bodily organs are composed of tissues, which are made of cells. The perfect machinery of the cells is controlled by our genes; i.e. DNA and RNA. Therefore, a minor defect or mutation in the genetic code may affect either partial or entire systems within the body. Some of these genetic diseases are inherited from our parents or relatives. Others may be introduced into our body through environmental mutagens, such as ionizing radiation, ultraviolet rays, or different chemicals within our food and drink; these can result in cancer or cardiovascular diseases. We can protect ourselves from the latter by using appropriate outfits, taking care with our diet, etc. However, inherited genetic disorders are usually unavoidable and sometimes have fatal consequences. Modern medicine is striving to find a way to treat these diseases. Although there are some medical procedures that may lessen the pain of patients or extend their life expectancy, there is no available comprehensive curative therapy for genetic disorders.

Gene therapy has become one of the rising stars in the field of molecular medicine during the last decade, with more than 1500 proposed or ongoing clinical trials worldwide. Gene therapy promises to provide curative therapies for a large number of inherited or acquired diseases, such as monogenic disorders, cancer, or cardiovascular disease. Gene therapy is universally defined as the replacement of an abnormal/dysfunctional gene in the cells of an individual with its correct and functional version. Mechanics use a number of tools to fix our cars for us when they give us trouble; in the same way, gene therapy can be used by doctors to alleviate or completely eradicate some diseases from our bodies.

Gene therapy is classified into two categories based on the target cells that are to be treated. The transduction of the differentiated cells of an individual, i.e. the somatic cells, is known as somatic gene therapy; the transduction of reproductive cells, i.e. gametes (sperm or ova), is known as germ-line gene therapy. Currently, there are many regulations in place that limit the likelihood of the modification of the germline in any gene therapy approach. This is because fear exists that the ability to alter the germline will result in the widespread application of gene therapy to achieve eugenic genetic enhancements, such as improvement of intelligence or physical characteristics. On the other hand, transgenic animals, which are used to detect the function of the genes within an organism, can be generated by modifying the germ-line. Furthermore, gene therapy is also classified into two groups: adult and fetal (in utero) gene therapy, according to the individual to be treated. There are several advantages and disadvantages to these methods, such as immune response, the pooling of mitotic cells, the amount of vector that is required, etc.; however, these are matters for a different article.

Gene therapy is achieved by using special exogenous genetic material transfer agents which are called vectors; these can be compared to the special tools used by auto mechanics. Over the years, a number of gene transfer vehicles, i.e. vectors, have been developed and these can be divided into two principal categories: non-viral (synthetic) and viral (virus-based) gene delivery systems.

Non-viral gene transfer can be achieved by using both physical and chemical methods. The physical methods include: i) Electroporation, in which areas of the cell membrane break down as result of an applied electric pulse, thus allowing DNA to enter the cell, ii) Ballistic gene transfer (the Gene Gun), which bombards particles coated with DNA into the cells, and iii) Microinjection, in which DNA is transferred through microcapillaries into the cells [1]. In terms of chemical gene transfer, lipofection is the most promising method; in this method negatively-charged DNA molecules bind to cationic lipid particles through electrostatic interaction and the DNA–lipid complex enters the cell through endocytosis/pinocytosis. Although these non-viral delivery systems exhibit low toxicity and can be easily produced in high concentrations on a commercial scale, in general, gene transfer using these agents is inefficient and often transient. Therefore, as a result of the viral vectors’ ability to efficiently deliver and integrate genes into the host genome, they are being engineered extensively to achieve a sustained and high-level expression of the gene of interest (transgene).

Viral vectors

Have you ever thought that one of the major pathological agents that cause catastrophic and even fatal diseases could be used to treat the same or a similar disease?

Viruses are equipped with specialized molecular mechanisms that allow them to efficiently transport the genomes into the cells they infect and use the cell’s machinery for their own reproduction. Molecular biologists first harnessed this machinery of transduction in the 1970s. Paul Berg used a modified SV40 virus containing DNA from the bacteriophage lambda to infect monkey kidney cells that were being maintained in culture. Viral delivery systems are based on replicating viruses that have the ability to deliver genetic information into the host cell, a process known as transduction [2]. Due to the fact that there are several advantages to viral vectors, these are the vehicles being employed in approximately 75% of all ongoing clinical trials worldwide. Numerous viruses are being used as the basis for the vectors, including, but not limited to, adenovirus (24%, n=377), retrovirus (20.9%, n=329), adeno-associated virus (4.3%, n=67), herpes simplex virus (3.2%, n=51), vaccinia virus (7.9%, n=124), poxvirus (5.8%, n=91), and baculovirus (more detailed information is available at www.wiley.co.uk/genmed/clinical). The first step to construct a viral vector for transferring the gene of interest involves the identification of the viral sequences that are necessary for replication and pathogenesis. Then some of the genes are removed to make room for the transgene and to render the viral vector replication-incompetent. Consequently, the vector is unable to replicate within the host, and therefore is safe for delivering genes to human cells or tissues (Figure 1).

There are advantages and disadvantages to all of the currently available vectors; the suitability of the vector, therefore, actually depends on the disease or condition that is being treated. For instance, if the goal of the gene therapy is to increase bone marrow engraftment with the transient expression of a growth factor, the use of chemical transfection or naked DNA transfer methods would suffice. However, if the objective is to provide long-term treatment for an inherited disease, then the use of an integrating viral vector is more desirable. Thus, a vector that might be ideal for treating one defect may not be ideal for another. Driven by the desire to develop the “perfect” vector, scientists are continually striving for novel forms of gene delivery that might become the “magic bullet.” Somia and Verma [3] have proposed that the ideal gene therapy vector should include all of the following properties: 1) easy production at a high titer on a commercial scale with a reasonable shelf-life for transport and distribution 2) sustained or regulated expression of the transgene product that is adjustable to the nature of the disease, 3) absence of immune response against the vector and the transgene product, 4) ability to target specific tissues and/or cell types while avoiding professional antigen-presenting cells, 5) absence of size limitations for the genetic material to be delivered by the vector, 6) site-specific integration of the transgene into the chromosome of the target cell to avoid insertional mutagenesis, or faithful division and segregation if it is to reside in the nucleus as an episome independent of local chromatin environments, and 7) an ability to infect dividing and post-mitotic cells. Unfortunately, none of the currently available gene delivery vectors carry all of these features; however, many vectors have enough of the attributes to make them promising for clinical use.

Candidate diseases

During the last 4 decades, gene therapy for many diseases has progressed from preclinical to clinical studies; these range from monogenic recessive disorders such as hemophilia and cystic fibrosis to more complex diseases such as cancer, cardiovascular disorders, human immunodeficiency virus (HIV), neurological and ocular pathologies. The prevalence of diseases that fall under the scope of gene therapy is enormous and most of them have catastrophic or fatal outcomes. Therefore, gene therapy approach for almost any of the diseases mentioned above has an obvious appeal and rationale. To date, more than 1,540 gene therapy clinical trials have been initiated, and these are continuing or have been completed in 28 countries, using more than 100 genes, including antigens, cytokines, tumor suppressors, growth factors, and deficiency genes [4].

Candidate monogenic disorders that are considered to be good candidates for treatment by gene therapy include the hemoglobinopathies, X-linked genetic disorders, amino acid metabolism disorders, and lysosomal and other storage diseases. Currently, there are more than 4000 monogenic diseases registered in the OMIM database. The ultimate aim in treating monogenic diseases with gene therapy is the correction of the disorder by the stable transfer of the functioning gene into dividing cells (stem/progenitor cells), which will ensure the permanence of the correction [5]. The first recognized successful clinical gene therapy trial involved the treatment of 11 children who suffered from SCID-X1 (Severe Combined Immunodeficiency), an X-linked inherited monogenic disorder caused due to a mutation in the common cytokine receptor gamma chain (γc). In these patients, immunity was not fully developed due to the blocking of T-cell and natural killer cell development as a result of mutation. Unfortunately, the trial in SCID-X1 also exemplified one of the potentially serious side effects of gene therapy. Three of the children developed uncontrolled clonal T-cell proliferation, that is, leukemia, almost 3 years after treatment. This case was associated with the integration of the retroviral vector close to the promoter of the LMO-2 proto-oncogene. As a result, LMO-2 protein expression was up-regulated in an abnormal way and resulted in leukemia [7]. Another candidate monogenic disorder for gene therapy is cystic fibrosis (CF), in which abnormally thick mucus is produced in the lungs of the patients, causing difficulty in breathing and increasing the frequency of serious lung infections. CF is known as the most common inherited genetic disease in Europe and USA, especially within the Ashkenazi Jewish population. The average life expectancy of patients with CF is less than 40 years; hence the treatment of this disease has become one of the prime targets of gene therapy research.

In addition to its use in the treatment of monogenic diseases, gene therapy is also becoming a therapeutic alternative for the treatment of various forms of cancer. Indeed, almost 65% of ongoing clinical trials are related to cancer (more detailed information is available at www.wiley.co.uk/genmed/clinical), an area in which much more promise can be seen; this is also a reflection of the urgent need for new therapies to tackle the escalating incidence of this disease. Several different principles are used to treat cancer, including gene therapy that is targeted at tumor suppressor genes, such as p53, or central signaling molecules, as well as “suicide gene” therapy, in which the transgene is capable of converting pro-drugs (selectively less active drugs) into drugs that are toxic for tumor cells. Furthermore, various gene therapy protocols have been developed to strengthen the host’s anti-tumor immune responses by immunotherapy. Most of these studies have been early clinical trials designed primarily as studies of the safety, applicability, and toxicity of gene therapy. Several of these phase I and II studies have, however, shown partial remission of tumors and, in rare cases, complete remission. However, complete cure of the tumor has not yet been achieved. In some trials, including TP53 gene therapy trials, regression in tumor size has been observed in up to 50% of patients. China has become the first country to license gene therapy as a regular treatment for neck and head cancer; here Gendicine, a replication-defective Ad5 vector expressing p53 from a Rous sarcoma virus (RSV) promoter, is used for therapy [6].

In addition to its applications for cancer and monogenic diseases, gene therapy has become one of the favorite methods in cardiovascular research field. This is in step with the rise in clinical trials for cardiovascular gene therapy from 8.3% to 9.1% during the last few years, becoming the second most popular application for gene therapy. In accordance with the variety and occurrence of cardiovascular diseases, different gene therapy strategies have been developed to tackle each disease on its own terms. The expectation is that gene therapy will provide a new avenue for therapeutic applications in the growth of blood vessels, as well as the protection, regeneration, and repair of heart tissue, the prevention of the reoccurrence of constricted or narrowed arteries following cardiovascular intervention, the prevention of the rejection of a bypass, and risk-factor management [4]. Long-term therapeutic gene expression is required in some diseases, such as hypertension research, where reversal and prevention are the key targets. On the other hand, for some other types of cardiovascular diseases, such as ischemia, atherosclerosis, and restenosis, shorter-term gene control will be sufficient to prevent further progress of the symptoms. Therefore, different gene-therapy vectors have to be considered for the treatment of each specific cardiovascular disorder.

Consequently, gene therapy offers new avenues of treatment for diseases including monogenic disorders, cancer, cardiovascular diseases, infectious pathologies and many more. As we follow the tradition, “God did not send down any illness for which He did not also send a cure (Bukhari)”, gene therapy using either viral, non-viral, or any other novel methods may pave the way for the cure of many diseases that are highly prevalent in the world and which for decades have been perceived as untreatable.

Dr. Ferhat Ozturk is a postdoctoral research associate at University of Nebraska Medical Center.

References

1. Wells DJ. “Gene therapy progress and prospects: electroporation and other physical methods.” Gene Ther. 2004 Sep;11(18):1363-9.
2. Kootstra, N.A. and I.M. Verma, “Gene therapy with viral vectors.” Annu Rev Pharmacol Toxicol, 2003. 43: p. 413-39.
3. Somia, N. and I.M. Verma, “Gene therapy: trials and tribulations.” Nat Rev Genet, 2000. 1(2): p. 91-9.
4. Edelstein, M.L., M.R. Abedi, and J. Wixon, “Gene therapy clinical trials worldwide to 2007–an update. J Gene Med, 2007. 9(10): p. 833-42.
5. http://www.biomedisch.nl/en/gene_therapy_targeted_diseases.php
6. Peng, Z., “Current status of gendicine in China: recombinant human Ad-p53 agent for treatment of cancers.” Hum Gene Ther, 2005. 16(9): p. 1016-27.
7. Cavazzana-Calvo M, Fischer A, Gene therapy for severe combined immunodeficiency: are we there yet? J Clin Invest. 2007 June. 117(6):1456-65

Some people might see me as a rough piece of flesh that wiggles in the mouth. Of course I am not that simple! By looking at my color, some experienced doctors can even diagnose an illness. For example, some well-known symptoms that I show are whitening due to fever, becoming dark brown when you have typhoid, blackening because of a yeast infection, or having a smooth surface because of anemia or lack of niacin (a B-group vitamin).

If you are wondering what my primary duties are, I can say that the first is to help to produce speech, an ability which distinguishes you human beings from animals. For sure this speech production is not only mine. First of all the brain, which is the coordinator of all the organs including me, regulates all my movements in speaking. The other organs that help me form sounds to make words are your teeth, lips, palate, the vocal cords in your throat, and your lungs, which work like an air pump and vibrate those cords. As you see, so many of us work together just to produce your speech.

Other than the speech function, my second major duty is to work as an inspector to taste and process the countless fruits and delicious foods that are given by God. That is how you get an idea about an animal- or plant-based substance that you want to eat. If I did not exist, you might die because of a poisonous plant that you ate out of hunger. Many poisonous substances have a bitter taste. Indeed, I can sense their bad taste the moment I touch them and warn you to spit out the thing in your mouth immediately. When you eat sweet and delicious things, however, I make you remember and thank God, who has given them to you. However, you should be careful about my fondness for taste and control yourself since that is part of a God-given test. My Creator has made a relation between my love of taste and the evil-commanding side of your soul. He has also made me a step for your spiritual development. If you eat and drink too much, which means you are misled by your evil-commanding side and abuse my sense of taste, it will be you who lose. I do what my duty requires and get the taste of everything. But it is your job to use your will power and not to be defeated by your evil-commanding self (nafs). I will never stop you, whether you eat one piece of baklava or ten; I will get the taste of every piece. Do not ever blame me for that!

I have another function that many people are not aware of. My movement causes a negative pressure in the cavity of the mouth. Are you wondering what this negative pressure does? This pressure is needed especially for babies to nurse on their mothers’ breast easily; I help them in the sucking movement. In addition to that, as everybody knows, I have very important functions in chewing and swallowing food. I manipulate the food in your mouth; I soften and moisten it with saliva so that it can be easily swallowed. Also, during swallowing, I move the food back toward the pharynx. I have to be very careful while doing all this, since at my smallest mistake, your teeth might bite and hurt me.

Of course, I can do all this only with the help of my Creator, who has built my anatomy of delicate tissues and cells. Since He never does anything absurd or useless, He has given every organ qualities that are both esthetic and functional. My main body consists of seventeen muscles, eight of which are in pairs. They extend in all directions. Among those muscles are the lipid membrane and some salivary glands. I am the most flexible organ in your body. My many strong muscles enable me to move in lots of directions easily. Those muscles are covered by an epithelial lining which is called the mucous membrane. The small projections on my upper surface are called papillae. These papillae are of several types. They contain receptors which allow you to sense taste and the salivary glands that help me stay wet all the time. The papillae cover as far as an A-shaped line towards my back which makes up a third of my length. Here at my back, there are plenty of salivary glands and the lymphoid tissue, also known as the lingual tonsil. Many germs that enter through your mouth get trapped here. The papillae are named according to their shapes. The filiform papillae (which are long and thin) do not contain taste buds. They only provide a rough surface to move the food easily. The food is moistened by your saliva and crushed by your teeth. Then, with the help of these papillae, I help to shape the food into smaller pieces to make it easier to swallow. The fungiform papillae are mushroom-shaped and scattered among the filiform papillae. They are located at the center of my top surface and they contain taste buds. The circumvallate papillae lie along the A-shaped line which makes up the border of my back. These papillae are larger in size and smaller in number; there are around thirteen of them. Each taste bud on the fungiform papillae has 50 to 75 receptor cells which live for only seven to ten days. When cells die because of hot or acidic foods, new ones are created to make new nerves for the taste buds. Only substances that are dissolved in water can reach the taste receptors. That is why I cannot taste a dry substance that you have taken into your mouth right away; it has to be moistened and softened first. Tasting occurs in the receptor cells of taste, where some analyses are undertaken much more delicately than in a chemistry laboratory. My receptor cells change this chemical stimulus into an electrical stimulus and send it to your brain. This electrical stimulus allows the sense of taste to be perceived.

Among the many kinds of taste, there are four major groups. The taste buds for sweetness are located near my front; the taste buds for saltiness are scattered widely on my surface; the taste buds for bitterness are found at my back; and the taste buds for sourness are on my sides.

My under surface extends between my tip and the floor of your mouth. The mucous membrane that covers this surface is smooth and does not contain papillae. It is purple in color because of the many blood vessels that are inside me and nourish me. By the way, the famous saying that “the tongue does not have a bone” is wrong, since I do have a bone. However, this bone is not located in my front body, which is why I am very flexible and I can say whatever you command me to say. But by my muscles and ligaments I am firmly bound to a U-shaped bone (the hyoid bone) at my root. I am connected to your lower jaw by this bone.

I can have disorders, like every other organ. In fact, many disorders in me are an indication of disorders in the other organs or of a metabolic illness. For example, mouth ulcers can often be seen on me. Some types of mouth ulcer are caused by stress, lack of sleep, or lack of vitamins. Others occur as a result of absorption disorders and as a symptom of Behcet’s syndrome. Some ulcers can last for weeks and they can be very painful. You might suffer from this pain especially when you speak and eat. Diseases such as syphilis and herpes also show themselves as ulcers on me. I might even become cancerous in people who smoke or in those who eat and drink things that are too hot. I sometimes show the symptoms of some metabolic disorders like Down’s Syndrome, the blockage of lymph vessels, glycogenosis and amiloidosis. In these disorders, my muscle mass shows excessive growth due to abnormally deposited glycogen and amyloid.

Dear Peter, until now, your “speechless organs” have talked about themselves in their own tongue. I have always talked, but I have always talked on your behalf, expressing your thoughts and feelings. It is you who are responsible for what I have said, good or bad, since I am bound to your will power. However, today I spoke in my own tongue, and on behalf of our Creator. As is well known, I am an organ that has great potential for both evil and good. It is your duty to control me and use me well. Do not ever forget that I am not a simple mass of muscle, epithelium and nerves. Rather, I am a tool that can be used for both debasing and elevating you. From now on, when you eat an apple, do not swallow it before chewing well; wait till I get the flavor of it very well. In that way, you will have an opportunity to thank God for the food you are given. He is the One who not only gave you that apple, but also me, the organ that can taste it. This is just another amazing thing that makes your life beautiful! By thanking God, you will deepen your worship of Him.

Irfan Yilmaz is a professor of biology at Dokuz Eylul University, Izmir, Turkey.