Every one of our five senses is unique in their own way. The miraculous sense of smell is pointed to in the famous story of Prophet Joseph when his father Prophet Jacob said, “I sense the fragrance of Joseph” from afar, and when he rubbed his shirt to his sightless eyes, he regained his sight (Qur’an 12: 94, 96). This suggests that smell, or sweat, may be a guide for researchers regarding the diagnosis and treatment of diseases.

Some of the novel characteristics of the sense of smell have recently been explored. Studies jointly conducted in three emerging disciplines, namely artificial intelligence (AI), nanotechnology, and molecular chemistry, have suggested that it may be possible to diagnose one’s diseases using the smells of his or her sweat, urine, and breath.

Imagine that Parkinson’s disease, multiple sclerosis, kidney failure, Crohn’s disease, pulmonary hypertension, chronic kidney disease, or any type of cancer could be diagnosed through a simple assessment of the smell of your breath without any painful procedure including having to insert a probe, syringe, or any other apparatus into the body. It would be so convenient, wouldn’t it? We know that breathalyzers are being used for many decades to detect drunk driving by analyzing the sample breath from a driver. Scientists have been curious as to why such an approach could not be utilized to detect other diseases in this manner and have thus engaged in an interesting research.

A team of researchers from universities in Israel, France, Latvia, China, and the United States have recently managed to diagnose 17 diseases with an accuracy rate of 86 percent using an analyzer that determines the molecules in breath samples with the help of AI software.

The scents that emanate from human bodies are as unique as fingerprints in that they are determined by genetics and metabolic differences among human beings. Human babies know their mothers from their scents, and they would not accept being nursed by a woman other than their mother unless they are extremely hungry. Every household has its unique smell. Couples know each other from the scents of their loved ones. The wise purposes for why such an abundance of smells exist in our lives include their whetting our appetite for eating food, feeling spiritual gratifications, and knowing and avoiding spoiled food and other potentially harmful substances. Evidently, when human health deteriorates, foul byproducts – such as the defective molecules that are the result of fermentation, death, decaying, or wrong synthesis due to faults in cells, tissues, or organs – start to move around the body through blood circulation. Some of these consequential defects are removed from the body via perspiration through the skin, urination through the kidneys, or exhalation through the lungs.

Molecular composition of breath

To better grasp this process, we need to have a closer look into the molecular composition of breath. When we exhale, we release nitrogen, oxygen, carbon dioxide, argon, and water vapor. Human breath also contains organic volatile chemical molecules in gas form that can readily blend into air due to having a high vapor pressure at a normal temperature. US biochemist Linus Pauling, one of the founders of modern quantum chemistry and molecular biology who won the Nobel prize in chemistry in 1954 and the Nobel peace prize, examined volatile substances in 250 samples of human breath using gas-liquid chromatography in 1971. Pauling is commonly regarded as a pioneer in the field of modern breath analysis. According to a study conducted 40 years later, exhaled breath contains more than 3,500 chemical compositions mostly consisting of trace amounts of volatile molecules [1].

Most of these compositions are metabolic products synthesized or decomposed based upon the functioning of the organism as a whole and some of them are called biomarkers. For instance, lung biomarkers are related to the processes that occur in the respiratory system, especially in one’s airways. Assessments of these biomarkers is useful in the diagnosis of inflammatory diseases of the respiratory system. Some examples of these biomarkers include hydrogen peroxide and isoprostans, nitric oxide derivatives, metabolites, inflammatory markers such as arachidonic acid (for instance, prostanoids, leukotrienes and epoxides), and adenosines. Breath temperature is also considered to be an important factor in prototypes of an “electronic nose” which takes all of these factors into consideration and in which new analytical and computer technologies integrate them together to produce unique results have started to be manufactured. In regards to diagnosing diseases through odor detection by animals, it is known that dogs are capable of diagnosing Mycobacterium tuberculosis, which causes tuberculosis, by smelling breath while rats can do it by smelling the sputum [2].

In a study, a blood sample taken from a patient with colon cancer was tested against blood samples from healthy subjects and a dog was able to diagnose the sample from the patient with cancer at every run. This study demonstrated that there is such a thing like the scent of a specific cancer and chemical compounds that are unique to cancers may be circulating in our body.

A research team led by professor Hossam Haick from the Israel Institute of Technology collected breath samples from 1,404 healthy people (control) and people suffering from 17 different diseases. These diseases included lung cancer, colorectal cancer, head and neck cancer, ovarian cancer, bladder cancer, prostate cancer, kidney cancer, gastric cancer, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, idiopathic Parkinson’s disease, atypical Parkinson’s disease, multiple sclerosis, pulmonary hypertension, preeclampsia toxemia, and chronic kidney disease.

The wet mucosa layer covering the insides of our nose typically attracts volatile chemical molecules. When odorant molecules come into contact with receptor cells located inside this mucosa epithelium, they become bound to these receptors and send electric signals to some 2,000 glomeruli, which are spherical structures consisting of nerves that can receive smells and encode them as electric signals in the olfactory bulb in the front and base of the brain. There are approximately 2,000 glomeruli around the surface of the center of the sense of smell. Smelling consists of interpretation of the patterns encoded based on the odorant molecules in these glomeruli. The human nose is capable of detecting one trillion smells. In Haick’s study, nanotechnology and machine learning replace the biological brain in the process of smelling.

Haick-led scientists used an organic carbon detection layer that controls the electrical resistance of layers made up of nanotubes through which nanotechnological molecules pass through in order to identify volatile organic compounds associated with specific diseases. The electrical resistance varies based on the type of volatile organic chemical molecules. AI software analyzes these changes in a machine learning system to determine which molecule occurs differently in ill people than healthy people in any specific disease. So far, gastric cancer was detected with an accuracy rate of 92-94 percent in the measurements made on more than 8,000 patients in clinics. Thus, researchers were able to discover that every disease has its own unique breath print [3].

As the diagnosis of diseases with the help of smell makes progress, the number of cases in which odor patterns in breath or sweat are determined increases. This raises the hope for detecting many diseases at an early stage even before their symptoms are manifest. An accuracy rate of 90 percent has been achieved in early diagnosis of preeclampsia, a disease associated with high blood pressure during pregnancy [4].

Dr. Hirsch says that the device that can diagnose lung cancer with an accuracy rate of 90 percent is able to detect a special “odor” coming from cancerous cells. The oily sebum secreted from the skin before any symptom of Parkinson’s disease has a musk-like scent which is not bad, but different from the normal. When physicians use the same technology to detect Parkinson’s disease, other cancers, kidney failure, multiple sclerosis, and Crohn’s disease, the accuracy rate is 86 percent. Ammonia in one’s breath is a sign of kidney failure. Researchers from the University of Illinois have developed a single-use device that can detect the breath print of kidney failure at a very early stage. There are even cases where doctors can diagnose certain diseases just utilizing their nose sensitivity without the need for special equipment. For instance, when a person’s liver starts to deteriorate and fails to decompose certain toxins these pollutants will accumulate in one’s urine, sweat, and even breath, and the odor of raw fish will be sensed.

If you have an infection in your gingiva, bacteria will secrete waste products that smells like rotten eggs due to hydrogen sulfide. This odor tells us that the person in question has gingivitis, a dental abscess, or poor oral hygiene. Diabetic patients have a fruit-like breath odor. This may indicate diabetic ketoacidosis as the body uses fats for energy due to a lack of sufficient insulin or lack of proper use of existing insulin. Sour breath is one of the early symptoms of infectious mononucleosis, caused by Epstein-Barr virus. In some rare metabolic diseases such as trimethylaminuria, foods such as fish, liver, eggs, and some vegetables cannot be digested in the intestines, and as they decay, they give off a strong “fishy” odor. In maple-syrup-urine disease, caused by a genetic disorder, infants are unable to decompose certain portions of proteins, and as a result, their urine, earwax, and other body liquids smells like maple syrup.

References

1. Popov, A. T. (2011): Human exhaled breath analysis. Annals of Allergy, Asthma & Immunology, Volume 106, Issue 6, p. 457.
2. Bijland, L.R., M K Bomers, M.K., Smulders, Y.M. (2013): Smelling the diagnosis: a review on the use of scent in diagnosing disease. Neth. J. Med.Jul-Aug. 71 (6): 300-307.
3. Nakhleh, M.K., Haick, H. et al. (2017): Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules. ACS Nano 2017, 11, 1, 112–125.
4. Nakhleh, M.K., Baram, S., Zaher, R.J. et al. (2016): Artificially Intelligent Nanoarray for the Detection of Preeclampsia under Real-World Clinical Conditions. Advanced Materials Technologies 1 (9): 1600132

Amyotrophic Lateral Sclerosis (ALS) is a terminal illness of the nervous system, resulting in the degeneration of neurons. When the motor neurons in the lateral spinal cord degenerate, the muscle cannot be stimulated and gradually atrophies. As the disease progresses, the brain cannot initiate and control muscle movement, so voluntary muscle actions, such as reaching for your phone or typing on a keyboard, are lost. Currently there are no treatments or cures to reverse the effects of ALS and the disease process is still widely unknown. Some noteworthy individuals diagnosed with this disease have included Lou Gehrig, Stephen Hawking, Jon Stone, George Yardley, Henry A. Wallace, and Steve Gleason. These are the facts, but I could have never realized what living with ALS was like until I listened to a retired senior, a teacher, and a musician tell me their stories.

The older couple told us of their past year as the husband wrote on an electronic note pad to fill in the gaps of his spouse’s version of their story. They had first noticed his symptoms when he began choking on his food, and they had to adapt as the disease progression got more and more severe. His wife comically said that she doesn’t know where to look when he’s trying to talk to her – “Should I look at his eyes, his mouth, this pad?” Every day, they had to face a new challenge and overcome it together, as a family.

Another patient was a mother, a teacher, now wheelchair bound and with a respirator to help her breathe. Because of her age, none of her physicians expected ALS and thought she was struggling from carpal tunnel syndrome or an ulnar nerve injury. She told us her husband was her biggest caregiver and supporter; her husband joked, “She makes the list and I carry it out.” He talked about his struggles, working full time as well as being a full-time caregiver for his wife and their 3-year-old daughter, as well as still finding time for self-care. Even with all this juggling, he felt guilty. This guilt was expressed by many of the caregivers: some because they didn’t even notice the symptoms and others because they felt like they couldn’t help their spouses. Guilt was felt by the patients too. The mother was upset because her daughter would only remember her in a wheelchair. Despite the difficulties, family was a major support system for each patient.

When asked about how she felt after getting her diagnosis, the musician said, “I felt like a deer in headlights… I never pictured I was going to go out that way… with a terminal illness… Last year I had no trouble walking, singing, cooking, gardening, and this year…” Despite all of this, she said she felt relieved. Her struggle to find a neurologist who respected her was heartbreaking. She had gone to a physician because she felt helpless; she was having trouble playing guitar, she was losing her identity as a musician. However, the physician assumed from her past medical history of anxiety that she was having mental issues with memory, anxiety, and depression. As she continued to receive hostile treatment, she found a second doctor who listened to her. Unfortunately, even though he took her seriously, he didn’t have the courage to diagnose her with ALS, telling her instead that she had a motor neuron disease and referring her to a specialist. When she finally received the diagnosis of ALS, she was relieved. She no longer felt crazy. She was able to be heard. She was able to communicate with someone who wanted to help her. ALS is already a hard disease to diagnose; not having someone on her side only made her situation more difficult. She says now, as each symptom appears, she isn’t afraid anymore, because she knows it’s ALS. This relief of having a concrete diagnosis, of having a diagnosable disease, even one that is untreatable, was reiterated by several of the other panelists.

Although a diagnosis was a relief for many of the patients, they all saw the importance of taking part in clinical trials. They recognized that ALS affects everyone at different times in different ways and hoped that one day they could explain why this illness is so hard to detect and track. Participating in various studies and trials made them feel like they were helping future patients and physicians to be able to better understand why this terminal disease can strike at any time, with no discernable warning signs, affecting each individual uniquely in initial symptoms and progression.

Getting a concrete diagnosis gave these patients the freedom to seize the day and live in the moment. For the musician, as her ability to play guitar diminished chord by chord, and she started slurring her words, preserving her voice and her identity became very important to her. She is using a message banking app to preserve her voice. The software requires her to read thousands of words and sentences. Although she had to accept the things she could no longer do, she realized that she did not have to give up her identity or love of music because of ALS. Overflowing with her love of music, she told us about how when choirs sings together, their hearts become synchronized; and how music lowers blood pressure and stimulates all areas of the brain. As she interwove details about her symptoms with her favorite song, Fire on the Mountain by the Grateful Dead, the two had become part of the same spiritual transformation. Smiling peacefully, she explained, “Maybe nobody else hears it the way I do. I see death as the final healing, finally being released from your body.” She viewed her diagnosis as graduating early and the symptoms that came attached with it as her disappearing slowly, rather than all at once. The unavoidable indignities were just something she had to accept. What mattered most to her was keeping her individual personality in the face of intense daily struggles.

By the end of our discussion, I felt the weight of my white coat as I never had before and recognized that this would be the first of many times that I would have to carry this symbol of patient advocacy. As these patients spilled all their vulnerabilities to a group of 50 students, I realized the most important thing I will learn in medical school is opening my heart without getting crushed under negativity. I learned that, as doctors, we have the tendency to think the ultimate solution is life, when in truth, mortality is the reality. What matters is being present when there is a fire, realizing that “a pail of water” may not be enough to put it out, but continuing to carry that water for your patient.

Long distance runner, what you standin there for?
Get up, get out, get out of the door

There’s a dragon with matches that’s loose on the town
Takes a whole pail of water just to cool him down
-The Grateful Dead

The examining of a disease was a hard process before the development of the imaging method. Medical professionals trusted the senses in their fingertips to examine if someone had a broken arm or leg. In time, scientists in different disciplines invented and improved technology to examine diseases by processing and verifying more precise data. Medical imaging is now one of the most improved techniques used for diagnosis of diseases, a technique used to create images of diseased parts of the body. After the discovery of the X-ray by German physicist Wilhelm Conrad Rontgen, the method of image creation started to take part in medical diagnosis methods in the first decade of the twentieth century. Recently, many different imaging techniques have been implemented for discrete diseases.

Nuclear medicine is a specialty area in medicine in which the energetic particles emitted from radioactive materials are used to diagnose and treat diseases. Short-lived isotopes are embedded into the human body and biologically active tissues absorb the embedded isotopes. This method is used to identify tumors and fracture points in bones. By using a technological device, the elementary particle photon is detected by sensitive detectors and then the data is converted into image. Gamma cameras capture the isotopes in the body to give a 2D image. The emitting of gamma rays is captured by sensitive detectors. This is generally how an imaging method works in nuclear medicine. What follows now is an overview of several imaging techniques and their advantages.

Magnetic Resonance Imaging (MRI)

MRI is one of the most common imaging techniques used to visualize the internal structure of the body by providing high quality images. This technique is based on the principles of the Nuclear Magnetic Resonance (NMR), which is a physical phenomenon in which absorption and emission of electromagnetic radiation by a nuclei in the magnetic field can be visualized. So, MRI provides an opportunity to observe the magnetic properties of the atomic nuclei of the human body. It has more advantages over other imaging techniques (such as Computed Tomography CT and X-rays) while observing the soft tissues of the body as brain, muscles and heart.

As many people may know, MRI consists of a large magnet which aligns the magnetization of the atomic nuclei and a radio frequency field which alters the direction of the magnetization routinely. Then, the 2D image of the body or a certain part of the body is recorded by a scanner.

Positron Emission Technique (PET)

One of the most accurate methods for diagnosing, staging and re-staging various kinds of methods is Positron Emission Tomography (PET). PET works as follows: a specified amount of radioactive substance is injected to the designated subject or a region of the body. When radioactive atoms decay, they release positrons. Positrons, antiparticles of electrons (+e), immediately collide with electrons (-e) and the annihilation process (+e + -e = photons) is formed and Gamma rays is produced. The emitted Gamma rays are detected by sensitive detectors and the image is constructed. PET is useful in receiving data about each organ of a body and their functions, and it is this data that is used to diagnose the disease. PET is very useful for studying the brain and its functioning and also provides a unique image of where the cancer cells are located in the body. Briefly, sugar molecules attached with radioactive isotopes are injected to the human body. Once doctors are sure that the sugar molecules are distributed to all parts of the body completely, the image is taken. Unhealthy cells eat up sugar molecules a lot faster than healthy cells. Then, only radioactive particles are left behind in the cancer cells which are exposed to the process explained above (+e + -e = photons). The formed gamma rays are detected and an image is formed.

However, it is really hard to localize the cancer cells when these cells are hand in glove with the soft tissues or hiding behind the skeleton. In that case, scientists compare the images by both PET and MRI to locate the cancer cells as precisely as possible. To treat a cancer cell precisely, this problem needs to be overcome first. Recently, particle physicists at the University of Oslo working at CERN [www.mergeous.com/articlecon.asp?aid=45] (the world’s largest particle accelerator) added a new dimension to this problem by inventing a new design of imaging technology. They combined PET and MRI in the same machine. They constructed a small PET machine which was able to be placed in an MRI machine. By doing this, they aimed to take two images at the same time, lowering the radiation exposure on people, and to decrease the statistical errors possibly made by the medical personnel when comparing the two images. Fortunately, they achieved their goals and invented a high sensitive and a low radiation machine. They improved upon new types of detector technologies by using photomultiplier tubes and light guide fibers. With these new detectors they were able to detect gammas more precisely and also to lower the image taking time. Erlend Bolle, a researcher in the field of high energy physics at the University of Oslo, said that [www.sciencedaily.com/releases/2012/08] they got this new detector idea from CERN which consists of several high tech-detectors.

Another practical application [www.mergeous.com/articlecon.asp?aid=45] of the particle accelerators is as follows: recently, a collaboration of researchers from Northern Illinois University (NIU) and particle physicists at Fermilab and Argonne National Laboratory have been trying to improve new detector technologies to have better 3D images of the human body to help cancer patients. Their aim [www.symmetrymagazine.org/article/april-2012] with this new particle detector was to attain better results by using protons for computed tomography (CT) instead of X-rays. A couple of years ago, the same group of researchers from NIU collaborated with a group of scientists from the University of California, Santa Cruz and Loma Linda University Medical Center to build a prototype proton system. They proved the advantages over the proton computed tomography to the X-rays CT. X-rays and protons show different characteristic properties when they get into the matter: X-rays start to give up their energy once they get into the matter. They affect healthy body parts like organs, tissues, cells, as well as tumors as they travel into the body. However, a proton behaves very differently to X-rays and it releases most of its energy at the end of its path. Because they do not deposit their energy along their path, they do not affect healthy tissues. By adjusting the speed of a group of protons, scientists can determine how long it goes on its path and where it deposits most of its energy to kill the tumor. This type of treatment can be a better option for soft tissues of the body such as the brain and pediatric tumors.

Sir William Henry Bragg, a British physicist and chemist, discovered the Bragg peak in 1903 which shows the energy loss of ionizing radiation during the particle’s travel into the matter. In Fig. 1 below, the vertical axis shows the dose produced by the proton beam when passing through the matter and the horizontal axis shows how far the proton beam goes before losing all of its energy. The figure illustrates two different kinds of protons produced by a particle accelerator of 250 MeV. As can be seen clearly in the figure, for protons, the Bragg peak occurs immediately before the protons come to rest. This means that they deposit most of their energy to their surroundings immediately before they come to rest. Therefore, this curve perfectly confirms that proton beams minimize the effect on surrounding healthy tissues. The purple line represents the photon beam, and it is clear that it deposits its energy gradually along its path.

Fig. 1: Brag Curve (reproduced from en.m.wikipedia.org/wiki/Bragg_peak)

There are many scientists from various disciplines working together to take science and technology one step further. As can be seen clearly in the work of cancer therapy with proton accelerators, if scientists from different unrelated disciplines come together and strive to advance technology to solve today’s problems, they could most probably overcome those problems and bring forward a new and problem-free world.

Kara is a freelance pop-sci writer pursuing a PhD in Physics.

]]> https://fountainmagazine.com/all-issues/1998/issue-23-july-september-1998/prenatal-diagnosis-watching-unborn-babies/ Wed, 01 Jul 1998 00:00:00 +0000 http://107.21.79.195/all-issues/1998/issue-23-july-september-1998/prenatal-diagnosis-watching-unborn-babies/ For many parents, pregnancy is an exciting and happy experience. For others, the experience of friends or family make them apprehensive that their baby may be born with a severe physical or mental disability. In fact, about one in forty babies will suffer from a congenital abnormality (Atkins and Hey, 1991). Abnormalities can range from something now correctable, like a cleft lip, to something severely disabling like congenital heart disease. Recent advances in medicine make it possible to give pregnant women a lot of information about their baby before birth. For the majority of parents- to-be prenatal testing (PNT) provides reassurance; for the minority the test results may indicate a problem with their baby’s growth or development.

There are many reasons why a developing baby may have congenital problems (Moore, 1989, p.lO8). Exposure to infections and certain drugs (most commonly, alcohol), chromosomal abnormalities and inherited congenital conditions have all been shown to disrupt normal fetal development. In this article we will concentrate on the diagnosis of chromosomal and genetic disorders during pregnancy.

PNT procedures and their interpretation can be extremely intimidating for parents. It is therefore important that tests are done only after a full explanation of the procedures involved and their possible consequences. The aim of PNT is to inform and prepare parents for the birth of an affected infant, so that they can choose between the possible courses of action (Aksoy, 1996). The possibilities will include: (1) in utero treatment; (2) delivery at a special centre for immediate postnatal treatment; and 3) termination of an affected fetus, i.e. abortion.

Over the years, professional standards and laws have evolved which influence the clinical application of PNT and help to tackle many of the complex ethical issues involved. There is little doubt that relatively non-invasive techniques whose primary purpose is to diagnose treatable disorders and then treat them, before or after birth, would be warmly welcomed by all, especially the parents. The fact is, however, that in practice PNT is generally being used to diagnose abnormality and then terminate the life of the unborn babies. The reality is that prenatal diagnosis rarely leads to fetal therapy

In what follows, we will try to explain the range of prenatal tests available and indications for their appropriate use. We will consider some of the technological advances on the horizon in this field of medicine, as well as some of the ethical dilemmas that arise.

Prenatal Diagnostic Tests

Prenatal diagnostic tests can be divided into two types, invasive and non-invasive. Non-invasive tests simply involve a blood sample taken from the pregnant woman or an ultrasound scan. Invasive tests on the other hand are more complicated and involve obtaining a sample of cells or tissue from the developing foetus, either by amniocentesis or chorionic villus biopsy. The samples obtained by invasive tests can be used, specifically to assess the fetal chromosome pattern, to determine if the fetus has a particular genetic mutation, or for a whole range of biochemical assays.

Maternal Blood Sampling. Between 15 and 19 weeks of pregnancy, the pregnant woman attending ante-natal clinic will be offered a blood test. The blood sample will be analysed to assess the level of three proteins, b human chorionic gonadotropin (b HCG), oestriol and a -fetoprotein (a FR). The three levels in combination with the mother’s age can be used to estimate the risk of the baby being affected by a chromosomal problem, especially Down’s syndrome (Wald and Cuckle, 1992, pS63). If the test result indicates a high level of risk, the mother will be offered further tests to assess the status of her baby.

Ultrasound Scan. Ultrasound uses high frequency waves to form a picture as the waves are reflected back by tissues of different density. The developing fetus grows in a liquid filled sac (amnion). As fluid shows black on the scan, this provides a good contrast with the fetal parts allowing high resolution images. Early in the first trimester an ultrasound scan can be used assess the viability of a fetus and to estimate its stage of development. Most women will be offered a formal high resolution scan at between 16 and 19 weeks (Sutton, 1990, pp.20- 1). The images from the scan will be the first time the expectant mothers see the baby. For many, this is a happy event; for the others it could be a very sad event if the scan indicates an abnormality.

Amniocentesis. In this test, done between 15 and 20 weeks of pregnancy (Cohen, 1990, pp.19- 20), a very fine needle is passed through the abdomen under ultrasound guidance, avoiding the fetus, and a sample of amniotic fluid containing fetal cells is withdrawn. The sample is cultured to grow more cells so that the chromosome pattern of the cells can be examined or DNA extracted for genetic analysis. This process can take three weeks, a period of considerable anxiety for the parents. There is also a small risk of miscarriage occurring after an amniocentesis.

Chorionic Villus Sampling. In this test, done in the same way as than amniocentesis but five weeks earlier, a sample of tissue is taken from the developing placental tissue. Both chromosomal and genetic analysis can be performed on this tissue, and the results are available quicker and at an earlier stage of the pregnancy than with amniocentesis. However, there is a higher miscarriage rate following chorionic villus sampling than amniocentesis (Boss, 1994).

Fetal Blood Sampling. Occasionally, when there is concern that a pregnant woman has been exposed to an infection early in her pregnancy, a sample of blood will be taken from the umbilical cord with a very fine needle under ultrasound guidance. This sample is used to assess if the fetus has become infected and at high risk of development problems following the maternal exposure.

New Advances

Advances in prenatal diagnosis have followed rapidly from technological improvements in ultrasound equipment, refinement and experience of current techniques, and the development of new tests. The aim of research in this area is to provide the earliest possible accurate information about the health of the developing baby, and to do so in the way safest for the expectant mothers and their babies. If the information is reassuring, the couple can enjoy the remainder of the pregnancy in the knowledge that everything will progress normally. However, if the result are unfavourable and an abnormality is diagnosed, earlier decisions about potential treatment or termination are possible and so may be less traumatic for those involved.

Fluorescent in situ Hybridisation (FISH). FISH is a technique which uses a specific DNA sequence as a probe to recognise its complementary sequence on a chromosome. The probe has a fluorescent tag attached which lights up when it is attached to the recognised chromosome segment. Recently FISH has been applied to analysis of amniocentesis samples to assess if an extra chromosome 21 is present or not in the cells. Because the amniocentesis cells do not require culturing for this technique the test results can potentially be available sooner than following standard amniocentesis.

Fetal Blood Cells in the Maternal Circulation. At about 6 weeks fetal blood cells can be found in a blood sample taken from a pregnant woman. These cells exists in very small numbers. Recent work has extracted and purified these cells to allow assessment of the fetal chromosome pattern and to determine if the fetus has a specific genetic mutation. Although this technique is very new it has the potential to make the currently used invasive techniques obsolete and will allow very early diagnosis.

Preimplantation Diagnosis. This procedure involves the use of technology developed with in vitro fertilisation (IVF). An oocyte is removed from the woman and brought into contact with spermatozoa from her partner under controlled conditions. One of the spermatozoa effects fertilisation to form a zygote. Following three stages of cell division (this eight-cell stage is termed, the blastocyst), one cell can be removed and used for analysis (Aksoy, 1997a). The DNA sequence of this cell can be determined to identify the presence or absence of a gene mutation that has caused illness in one of the parents. If the cell does not contain the mutation, the blastocyst can be implanted in the womans uterus (womb) to develop into a fetus which is unaffected by the condition that has affected other family members.

Human Genome Project. The aim of the Human Genome Project is to have identified the entire human DNA sequence (genome) by 2005. The extra information generated about specific genes and their association with specific disorders has the potential to expand dramatically the number of genetic tests available to couples with a family history of a genetic condition.

Ethical Issues

It is important to understand the purpose of prenatal diagnosis. It is done to provide parents with information about the health and development of their baby, not to provide them with a reason to have a termination of pregnancy. There are 180,000 terminations performed each year in the United Kingdom, of these 5000 are because of fetal abnormalities diagnosed by prenatal tests. Abortion is a serious problem itself in all regions of the world, developed and developing, and we discussed it in an earlier issue of this magazine (Aksoy 1997b). When prenatal tests reveal that a baby has health problems, parents face a number of difficult questions. Is any treatment available? What are the baby’s chances of survival? What would be the baby’s quality of life if he or she did survive? Some illnesses can be treated during pregnancy and after delivery. One of the main aims of fetal medicine is to develop therapies to treat fetuses and improve the survival. However, some conditions are fatal despite all treatment. In these circumstances couples sometimes take the extremely difficult decision to have a termination of pregnancy

For religious, moral or other reasons many couples opt not to have any tests performed during pregnancy. They feel that even if the results of any test indicated that their baby was affected by a serious condition they should and would continue with the pregnancy. It is important in each situation that the parents’ decisions are respected and supported. The parents need to be given appropriate guidance and counselling rather than be met with disapproval.

In some countries prenatal testing has been extensively used to determine the sex of the baby at an early stage, with the intention of ensuring that only male babies are born (Kusum, 1993). In the United Kingdom, as in many other places, prenatal diagnosis to determine fetal sex is deemed morally unacceptable. It is important that new advances in medicine are paralleled by an informed ethical debate. Prenatal tests should reflect what is appropriate within a society rather than just allowing what is technically feasible. A number of regulatory groups have been formed, including the Human Fertilisation and Embryology Authority (HFEA), to monitor and regulate new advances in this area.

In sum: prenatal diagnosis is a rapidly expanding area of medicine. New techniques are constantly being developed which are aimed at allowing earlier diagnosis, less invasive methods and, ultimately, treatment. It is important that developments are monitored and regulated to ensure that the techniques available are applied within an ethical framework.

REFERENCES

Aksoy, S. (1996) ‘Prenatal Testing: An Ethical Perspective’, The New Journal of Medicine, 13:2, pp.12-14.

Aksoy, S. (1997) ‘Moral Controversies on Preimplantation Genetic Testing’, paper presented at UNESCO Asian Bioetlncs Conference, Kobc-Japan, November 1997.

Aksoy, S. (1997), ‘Abortion: Mercy or Murder?’, The Fountain, 2:17 pp.32-5.

Atkins, A.F.J. and Hey, EN. (1991) ‘The Northern Regional Fetal Abnormality Survey’, in Drife, jO. and Donnai, D.(cds) Antenatal Diagnosis of Fetal Abnormalities, Springer-Verlag Ltd., London.

Boss, J.A. (1994) ‘First Trimester Prenatal Diagnosis: Earlier is not Necessarily Better’, JME, 20 pp.l46-5l. )

Cohen, L.G. (1990 Before Theýr Týme at Risk, American Association on Mental Retardation, Washington DC.

Kusum (1993) ‘The Use of Pre-natal Diagnostic Techniques for Sex Selection: The Indian Scene’, Bioethics, 7: 2/3 pp,149-65.

Moore, K.L. (1989) Before We Are Born: Basic Embryology and Birth Defects, WB. Saunders Comp., Philadelphia.

Sutton, A. (1990) Prenatal Diagnosis: Confronting the Ethical Issues, The Linacre Centre, London.

Wald, NJ. and Cuckle, H.S. (1992) ‘Biochemical Screening’, in Brock, D.J.H., Rodeck, C.H. and Ferguson-Smith, MA.(eds) Prenatal Diagnosis and Screening, Churchill Livingstone, Edinburgh.

Genetic counselling is the process whereby an individual or family obtain advice and information about a genetic condition that may affect the individual and family, their children and the wider community. The aim of such counselling is to enable appropriate decisions to be taken regarding marriage, reproduction, abortion, and health management.

Islamic teachings encourage counselling. The Prophet Muhammad, upon him be peace and blessings, said: The religion (i.e. Islam) is sincere counselling and good advice (Bukhari, Muslim). He also said: The counsellor should be trustworthy. Genetic counselling is a new field of medical practice that demands extensive knowledge of genetics, the management of genetic disease and how it impacts on the individual, the family and the community at large. The counsellor must therefore be knowledgeable in the field, otherwise he will be answerable. The Prophet said: If a person practises medicine without appropriate knowledge, then he is liable (Abu Dawud). Experts in Islamic law explain that the person must be proficient in the particular field of medicine he is practising; it is not sufficient to know general medicine, the person must have obtained the appropriate specialist training. The Prophet said: No man is wise except through experience (Bukhari, Muslim).

In addition to knowledge and proficiency, the counsellor needs also to be considerate, compassionate and able to guard the confidentiality of the information he is given. The Prophet said: Whoever guards the secrets of a Muslim, God will guard his secret in this life and on the Day of Resurrection (Muslim). And: God will show mercy to those who are merciful to people (Bukhari, Tirmidhi, Ahmad, and others). Being considerate and kind, and giving good advice to those who seek it, is the basis of Islamic ethics in general and medical ethics in particular. The worst thing of all is doing harm intentionally or even unintentionally, the former being a crime and the latter an offence. This rule is derived from the explicit injunction of the Prophet: Do no harm nor return harm with harm (Abu Dawud).

The genetic counsellor may not impose his views on his clients. Rather, he must let them reach their own decisions. The counsellor’s responsibility is to enable his clients’ responsibility by providing them with the necessary facts and information in plain language that they can understand easily and fully.

The Islamic creed places the highest value on personal freedom and hence upon personal responsibility for one’s actions. The genetic counsellor should therefore provide the best available information, and then give the most sincere advice without trying to impose it: the clients must reach any decision themselves.

Genetic diseases

Monogenic diseases, i.e. diseases inherited through one gene, constitute only 10-15% per cent of congenital diseases and malformations in the population as a whole, but account for a much larger percentage of childhood diseases: in many Western countries, for example, some 50% of all deaths of children up to age 15 are attributed to hereditary factors.

Many of the most common diseases world-wide, e.g. diabetes mellitus, hypertension, ischaemic heart disease and cancer, have a hereditary component. Many neurological and psychiatric ailments are either monogenic hereditary diseases or heredity is a major causative factor. Similarly, diseases of the blood are either directly caused by a monogenic hereditary factor, or other hereditary factors have a major causative role. Thalassemia and sickle cell anaemias are examples of autosomal diseases that cause malady and high morbidity in many countries, notably in the Mediterranean and Arab world.

Close-cousin marriages and their consequences

Consanguine or close-cousin marriages are commonplace in most Arab countries. The incidence of genetic diseases is correspondingly high; for example, 5-10% of the population as a whole carry the gene for thalassemia. Islamic teachings do not forbid but do discourage first cousin marriages – i.e. insofar as they are permitted at all, such marriages are only allowable exceptionally, not encouraged as the norm. It is narrated that when it was brought to the attention of ‘Umar ibn al Khattab, the second Caliph, that the children of the Bani Assayib were often weak and sickly, he advised this tribe to avoid close-cousin marriages and to seek spouses for their children from remote tribes; he said: ‘Marry from remote tribes, otherwise you will be weak and unhealthy.’

Responses in the Arab world

In the first half of this century, many Arab governments (Egypt, Syria, Lebanon, Tunisia, Morocco and others) made a premarital medical examination mandatory. However, this had little effect on the incidence of consanguineous marriages or hereditary diseases as there were no means for searching out carriers of genetic diseases. In any case-as we are bound to note with deep regret-a medical certificate was often provided without even a routine medical examination.

Several recent symposia (for example, in Amman, Jordan, 10th August 1994) have discussed the implementation of a law making it obligatory to test for the thalassemia gene as a precondition for granting a marriage license. However, there are immense difficulties with this policy. The cost of such a test would be huge. Who would bear the cost? Most governments could not do so, and if they could, it would be by diverting funds from other more urgent medical needs. Individual citizens might decline the test or evade it on the grounds of poverty. If made compulsory, it is possible that medical certificates might be forged or false certificates sold for money. More serious is the question of personal autonomy: even if such tests could be funded and carried out with integrity, who could compel a couple, either or both of whom showed positive, not to marry? Attempting to do so would surely be, if at all practicable, wholly unethical.

In the case of such a couple, a number of alternatives might be put to them:

1. contraception or sterilization to avoid pregnancy;
2. adoption;
3. donation of a sperm or ovum or pre-embryo;
4. pre-implantation diagnosis;
5. diagnosis during pregnancy (e.g. chorion villus sampling, amniocentesis, blood tests from the expectant mother and the foetus, ultra sonography, etc.)

Each of these procedures needs to be scrutinized from an Islamic perspective:

1. Contraception and sterilization

Contraception is allowable under Islamic law as a temporary measure if the couple decide upon it and if there is no harm from the particular method used. Sterilization, however, is not acceptable unless there is danger to the mother’s health from pregnancy. Most couples long to have children and will not choose sterilization unless there is a serious impediment preventing safe procreation in their case. As infertile couples are willing to pay out huge sums of money and go to great lengths to have a child, it is impractical to expect couples carrying a recessive gene such as for thalassemia to opt for sterilization. Everyone of us carries some recessive genes and no-one will choose celibacy or sterilization for that reason alone.

We may note that there is support for sterilization from at least some of our jurists in the situation where a couple have already had some congenitally affected children and some not so affected, in which case they might accept this option.

2. Adoption

Adoption was abrogated by the Qur’an, and in Islamic law adoptive parents are not recognized as parents in the way that natural parents are. The child must be attached in lineage to his or her natural parents, and legitimate pregnancy is, according to the law, only within wedlock. The Qur’an says:

He did not make your adopted ones your sons. That is only a saying from your mouths which has no reality. Call them by [the names of] their [true] fathers. That is just in the sight of God. But if you do not know their fathers, call them your brothers in faith or your mawlas. There is no blame on you if you are mistaken. What counts is the intention of your hearts, and Allah is oft- forgiving and most merciful. (33, 4-5)

Bringing up orphans is a highly commended act of charity, encouraged by Islamic teachings, but even then the lineage of the child must remain to his or her natural father. Therefore, while a couple who are carriers of a lethal gene or a gene that carries a risk of great malady and morbidity for their offspring cannot become natural parents, they can nevertheless adopt one or more orphans in the sense that they can look after and care for them and have all the rewards of bringing them up.

3. Donation of a sperm, ovum or pre-embryo

In the West, a new technology of procreation is being made available to infertile couples. This technology, making use of semen banks and in vitro fertilization techniques, may involve donated sperm or ova, a donated pre-embryo (blastula or morulla), or, in the case of surrogate motherhood, a None of this technology is acceptable in the view of Islamic teachings which recognize procreation only within the bounds of wedlock excluding any third party from the process. Therefore, a Muslim couple who are carrying a lethal gene or serious disease gene cannot make use of either donated sperm or ova or pre-embryos or surrogate motherhood. These methods are refuted by all Islamic jurists on the grounds that procreation must be limited to the spouses alone, without the intervention of third parties.

4. Pre-implantation diagnosis

Advances in medical technology over the last decade or so have made it possible, at least in some specialist clinics, to remove one or more cells from donated womb, the blastula (pre-embryo) prior to its implantation in the womb. A husband’s semen is allowed to fertilize in vitro the ovum taken from his wife; when fertilization occurs, the zygote is allowed to grow to the blastula or morulla stage – this happens a few days after fertilization. If genetic disease or chromosomal abnormality (e.g. triosomy 13, 18 or 21) is suspected, one or more cells are taken from the blastula for appropriate testing. If the blastula is shown to have the defective gene or chromosome, it is discarded and another one tested. Only the unblemished blastula is reimplanted.

The main disadvantage of this technology is the low rate of success after reimplantation (pregnancy rate 30% in the best centres; while take-home-baby rate is around 15%). The merit of the method is that it avoids abortion. The technique is also paving the way for gene therapy and manipulation at an early stage: as yet unfeasible, this will surely be possible in the near future. However, along with the technical problems facing gene therapy, there are also a number of ethical problems (see below).

5. Diagnosis during pregnancy

Better and more accurate diagnoses of congenital malformations, genetic diseases and chromosomal abnormalities are becoming available with the tremendous advances in medical technology.

Simple blood tests from the expectant mother can help the diagnosis of, for example, alpha feto proteins in cases of neural tube defects, viz. anencephaly and spina bifida. Ultrasound can detect many dysmorphic abnormalities as well as congenital defects of the heart, brain and kidneys. CVS or chorion villus sampling, which can be done during the 8th week of pregnancy, can detect genetic and chromosomal defects when suspected. So too can amniocentesis but at a much later stage of pregnancy, between the 14th and 16th weeks. The advantage of early diagnosis by CVS is offset by higher percentage of abortions and complications (2-3%), compared to amniocentesis which is safer albeit giving a much later diagnosis. The couple are offered the choice of abortion when a serious congenital or hereditary disease is discovered.

The Islamic Jurisprudence Council of the Islamic World League in its 12th session (Makka, 10- 17 February 1990) agreed a fatwa by majority vote which allows the option of abortion to the parents on the condition that the pregnancy is less than 120 days old (computed from fertilization and not last menstrual cycle); that a committee of specialist experts have decided that the foetus is grossly malformed and that its life would be a calamity for the foetus and for the family; and that the malformation is very serious and neither treatable nor manageable. On the basis of this fatwa, abortions of foetuses with serious congenital diseases are carried out in the hospitals in Saudi Arabia.

Unanswered ethical questions and dilemmas

There are many dilemmas. Is it allowable to abort a foetus showing Downs syndrome although even with this condition it is possible to live a quiet, peaceful life? If the Huntington’s disease gene is detected, is an abortion justified, although the disease will not appear until age forty or even sixty? Is it permissible to abort those who are homozygous for sickle cell disease or thassalemia or phenyl ketonuria or homocystinuria? For the last two diseases mentioned there is a treatment, namely to avoid foods that contain phenyl alanine or methionme. There is some treatment possible also for the haemolytic anaemias, namely blood transfusion and iron chelation therapy (desferrio-xamine injections).

It is greatly to be hoped that in the not too distant future advances in gene therapy will remove the need to consider abortion in such cases. In the meantime, the best policy is to encourage couples considering marriage to have pre-marital medical examinations for the infectious and hereditary diseases common in their community. It is also important to educate people more effectively and actively about the dangers of consanguineous marriages which, as noted earlier, are very common in most Arab countries.