The global demographic population is ageing at a rapid pace. In the UK alone, one-fifth of the population, roughly 11.8 million citizens are more than 65 years of age or older. This ever-growing elderly population suffer from multiple chronic diseases (multimorbidity) such as cardiovascular disease, osteoporosis and dementia. Although there has been an increase in life expectancy, the vast majority tend to live in ill health over the course of their lives. As a result, there is increased need for hospital visits and hospitalisation, placing a huge burden on the healthcare system.
 
Polypharmacy, the use of multiple drugs or more than medically appropriate, is a burgeoning concern amongst older patients with multimorbidity. The research undertaken by the National Institutes of Health has shown that polypharmacy has become increasingly and alarmingly common in older adults with the highest number of drugs taken by those residing in nursing homes. Nearly 50% of the elderly population take one or more medications that are not medically necessary. The increased use of polypharmacy by doctors and over-prescription of unnecessary medications leads to drug to drug interactions contributing to the increased risk of falls in the elderly population, delirium and other related healthcare complications. Current evidence in medical literature clearly establishes a strong link between polypharmacy and detrimental clinical consequences in later life. Due to this, hospitals see an increased number of hospital admissions and re-admissions. This increased healthcare demand places undue strain on NHS healthcare workforce and infrastructure leading to a supply and demand mismatch.
 
The advancements in digital health technologies such as Telemedicine and Artificial Intelligence (AI) has contributed to the use remote-monitoring devices in elderly patients. AI technologies and interconnected personal devices has made it possible to audit, analyse and assimilate extensive medical data throughout the elderly population. A research conducted by Professor Arnold Milstein at Stanford University using thermal imaging cameras and AI algorithms has identified patients at risk of falls and injuries in community thereby preventing these by district nurses visiting their homes before an event. The use of thermal imaging and other medical technologies has proven to show the reduction in hospital admissions due to prophylactic interventions beforehand and early treatment of infections such as urinary tract infections. This has also assisted remote monitoring of ageing and vulnerable patients, and has delivered highly targeted and direct diagnostics, healthcare and treatment. The use of technology in healthcare and AI has opened up access to personalised and precision medicine.
 
The ongoing Covid-19 pandemic has pushed digital technology into the forefront of medicine through virtual clinics and telemonitoring of patients who are unable to visit hospital due to self-isolation and distancing measures. Broader use of this technology in the daily lives of elderly patients will help to identify those patients in need of help before they become unwell and needing hospital care. The use of Artificial Intelligence and remote monitoring of patients using advanced digital health technology will undeniably revolutionize healthcare delivery in the future by taking hospital care to the doorstep of communities. 

The technology involved in genetic editing has made huge breakthroughs in the past few years. What began as an unrealistically difficult and ambitious endeavour in the increasingly complex world of medicine has now manifested into a reality through technology such as CRISPR. Genetic editing holds the power to not only treat but prevent countless diseases, transforming the world of medicine and possibly even diverging the path of human evolution itself.

The debate as to whether genetic editing is justified has been fiercely battled for years. The first genetically edited babies were born in China in November 2018. The scientist responsible for this, He Jiankui, was found guilty of “illegal medical practices”. He served three years in prison and was fined a huge 3 million yuan (£327,360). The Chinese court even insisted Jiankui “crossed the bottom line of ethics in scientific research and medical ethics.” Large numbers of people agree with this claim, arguing genetic editing can never be justified.

The main reasons supporting this argument include how genetic editing involves humans ‘playing God’. Religious believers often insist that only God should have the right to edit such a crucial element of our individuality, and humans should be happy with their genetic identity as it is ‘God’s gift’, even if this genetic identity involves a disease.

The misuse of genetic editing has been a cause of much concern. Its potential use to enhance characteristics such as physical strength, looks, or even intelligence would be unfair to ‘unedited humans’ and possibly biased to the wealthy- the poor will likely be unable to afford genetic editing. A ‘black market’ related to gene editing - much like ‘back alley ’abortions - may develop, where those who cannot afford gene editing will choose unauthorised and unregulated facilities with likely higher complication rates due to the lack of sanitation and doctors able to preform the procedure.

Furthermore, if everyone decides to genetically edit themselves there would be a reduction in genetic variation in the human species. Further concern is that eradicating genetic diseases would result in overpopulation, thus greatly contributing to the ever worsening issues of global warming and depletion of essential natural resources.

There is also a strong ethical issue associated with all types of gene editing – is it really correct for people to use the system to ‘customise’ their own children? Surely only the child should have the right to alter their appearance and should do it when they are old enough to understand the significance of this irreversible decision.

Genetic editing may gives rise to eugenics in dictatorship countries - where political or government groups forcefully try to modify the gene pool of some of their subjects. This may be to ensure mental and physical advantage in warfare or scientific careers.

In addition to ethical issues and the potential misuse of genome editing, there are concerns over safety and possible complications. Germline therapy (a type of genetic editing where DNA is transferred into the cells that produce reproductive cells) poses a potential infection risk through the use of viral vectors that enable DNA to be transferred into these cells. No one can truly predict how these resulting genes may interact during fertilisation and what genetic defects may arise.

On the other hand, one can argue that genetic editing can easily be justified. After all, a long time ago surgery would have been considered as a human taking the opportunity to ‘play God’. Surgery was previously extremely risky due poor hygiene, little access to powerful anaesthetic and sub-optimal techniques with high complication rates. However, surgery is currently much safer- millions of people undergo it and change their lives for the better. Many people predict this future for gene editing – there is nothing wrong with people wanting to rid themselves of a disease to empower themselves and become healthy again- we all have the right to be as healthy as possible. Nature can be very cruel to us- people cannot choose whether they end up with genetically inherited diseases such as haemophilia which completely destroy one’s life and damage their mental health as well as their physical health. If research in genetic editing continues we will have the power to live long and happy lives. Couples can be reassured that their unborn children can too since germline therapy ensures the disease will not be inherited in the family again.

If gene editing becomes widespread and advanced enough it will be the key to controlling human evolution – humans will eventually be much more intelligent creatures who are more mentally and physically resilient to the variety of challenges life brings in our day to day lives. In fact, instead of waiting hundreds of thousands of years for beneficial mutations to arise (as with natural selection), we could start to see beneficial changes every year. Many people regard gene therapy as unsafe, however, as with all new therapies, medicine, and vaccinations, genetic editing will be vigorously tested and researched before it is released to the public as a standard procedure, certifying its safety.

In conclusion, genetic editing could greatly benefit people, increase longevity, and change the scale of human happiness and productivity by multiple orders of magnitude. It could eliminate thousands of diseases and many forms of pain and anxiety arising from them. There are only a handful of areas of research in the world with this much potential. However, whilst it may be a wonderful addition to medical science, there needs to be firm monitoring to ensure genetic editing is as risk free as possible. Furthermore, it must be strictly controlled to avoid misuse. Genetic editing has risks- we must proceed with caution, but many new technologies have risks and we are eventually able to use them to greatly benefit people throughout the world. We should not let fear hold back progress on this extremely promising new area of research.

​Introduction:
 
As a second patient is seemingly cured of HIV after receiving a stem-cell treatment for his (Hodgkin lymphoma) cancer, it begs the question of whether HIV is ‘incurable,’ as we have always assumed. This article will endeavour to explain how HIV and AIDS affect the human body, how Adam Castillejo was ‘cured’, and what all this means for the future of modern medicine.
 
HIV:
 
HIV stands for the human immunodeficiency virus. It is a virus that attacks cells that would normally help the body fight infection (CD4 helper cells), making a person more vulnerable to other infections and diseases. CD4 helper cells are a subset of white blood cells that do not neutralise infections, but rather trigger the body’s response to infections.
 
There are 7 steps that HIV follows to multiply in the body. These are illustrated in the picture below. The process begins when HIV encounters a CD4 cell. The 7 steps in the HIV life cycle are

1. Binding. HIV binds to receptors on the surface of a CD4 cell.
2. Fusion. The HIV envelope and the CD4 cell membrane fuse (join together), which allows HIV to enter the CD4 cell.
3. Reverse Transcription. Inside the CD4 cell, HIV releases and uses reverse transcriptase (an HIV enzyme) to convert its genetic material- HIV RNA- into HIV DNA. The conversion of HIV RNA to HIV DNA allows HIV to enter the CD4 cell nucleus and combine with the cell’s genetic material- cell DNA.
4. Integration. Inside the CD4 cell nucleus, HIV releases integrase (an HIV enzyme.) HIV uses integrase to insert (integrate) its viral DNA into the DNA of the CD4 cell.
5. Replication. Once integrated into the CD4 cell DNA, HIV begins to use the machinery of the CD4 cell to make long chains of HIV proteins. The protein chains are the building blocks for more HIV.
6. Assembly. New HIV proteins and HIV RNA move to the surface of the cell and assemble into immature (non-infectious) HIV.
7. Budding. Newly formed immature (non-infectious) HIV pushes itself out of the host CD4 cell. The new HIV releases protease (an HIV enzyme). Protease breaks up the long protein chains in the immature virus, creating the mature (infectious) virus.

Not only does HIV attack CD4 cells, but it also uses the cells to make more of the virus. HIV destroys CD4 cells by using their replication machinery to create new copies of the virus. This ultimately causes the CD4 cells to swell and burst. Once the virus has destroyed a certain number of CD4 cells and the count drops below 200, a person will have progressed to AIDS.
 
You can get or transmit HIV through specific activities only. Most commonly, people get or transmit HIV through sexual behaviours and needle or syringe use. Only certain fluids- blood, semen, rectal fluids, vaginal fluids, and breast milk- from a person who has HIV can transmit HIV. It can also be transmitted from mother to baby during pregnancy via the placenta.
 
AIDS:
 
AIDS is the acquired immune deficiency syndrome. It is the name used to describe a number of potentially life-threatening infections and illnesses that happen when your immune system has been severely damaged by the HIV virus. Many people often confuse HIV and AIDS- HIV causes AIDS. HIV destroys CD4 T cells- white blood cells that play a significant role in helping your body fight disease. The fewer CD4 T cells you have, the weaker your immune system becomes. You can have an HIV infection, with few or no symptoms, for years before it turns into AIDS. AIDS is diagnosed when the CD4 T cell count falls below 200, or if you have an AIDS-defining complication, such as a serious infection or cancer. Thanks to better antiviral treatments, most people with HIV today don’t develop AIDS. Untreated, HIV typically turns into AIDS in about 8-10 years. AIDS only occurs once your immune system has been severely damaged and as mentioned before, is only diagnosed once the CD4 T cell count falls below 200, or if you have an AIDS-defining complication.
 
TREATMENT:
 
Antiretroviral medicines are normally used to treat HIV. They work by stopping the virus replicating in the body, allowing the immune system to repair itself and preventing further damage. These come in the form of tablets, which need to be taken every day. HIV is able to develop resistance to a single HIV medicine very easily, but taking a combination of different medicines makes this much less likely. On top of this, there are some people who are actually naturally resistant to HIV. CCR5 is the most commonly used receptor by HIV-1- the virus strain of HIV that dominates around the world- to enter cells. But a small number of people who are resistant to HIV have two mutated copies of the CCR5 receptor. This means the virus cannot penetrate cells in the body it normally infects. Researchers say it may be possible to use gene therapy to target the CCR5 receptor in people with HIV. Adam Castillejo was the second patient to be cured of HIV. He received a stem-cell treatment for a cancer (Hodgkin lymphoma) he had, and this rendered him virus-free. This is because the donor of the stem cells had the uncommon gene that gives them and now Mr Castillejo protection against HIV.
 
STEM CELLS:
 
In order to understand how the phenomenon of Mr Castillejo becoming HIV free came about, it is important to look more closely at how stem cells work. Stem cells are special human cells that have the ability to develop (differentiate) into many different cell types, from muscle cells to brain cells. In some cases, they also have the ability to repair damaged tissues. Stem cells are divided into two main forms- embryonic stem cells and adult stem cells. The embryonic stem cells used in research today come from unused embryos resulting from an in vitro fertilisation procedure that are donated to science. These embryonic stem cells are pluripotent, meaning they can turn into more than one type of cell.
There are two types of adult stem cells. One type comes from fully developed tissues, like the brain, skin, and bone marrow. There are only small numbers of stem cells in these tissues, and they are more likely to generate only certain types of cells. For example, a stem cell derived from the kidney will only generate more kidney cells. The second type is induced pluripotent stem cells. These are adult stem cells that have been manipulated in a lab to take on the pluripotent characteristics of embryonic stem cells. Although induced pluripotent stem cells don’t appear to be clinically different from embryonic stem cells, scientists have not yet found one that can develop every kind of cell and tissue.
The only stem cell currently used to treat disease are hematopoietic stem cells- the blood cell-forming adult stem cells found in the bone marrow.
 
Stem cell transplants are used currently in the treatment of cancer. In a typical stem cell transplant for cancer very high doses of chemotherapy are used, sometimes along with radiation therapy, to try to kill all the cancer cells. This treatment also kills the stem cells in the bone marrow. Soon after treatment, stem cells are given to replace those that were destroyed. These stem cells are given into a vein, much like a blood transfusion. Over time, they settle in the bone marrow and begin to grow and make healthy blood cells. This process is called engraftment.
 
There are two main types of stem cell transplants.
 
Autologous stem cell transplants are when the stem cells come from the same person who will get the transplant. In this type of transplant, your own stem cells are removed, or harvested, from your blood before you get treatment that destroys them. Your stem cells are removed from either your bone marrow or your blood, and then frozen. After you get high doses of therapy, the stem cells are thawed and given back to you. One advantage of autologous stem cell transplant is that you’re getting your own cells back. You do not have to worry about the new stem cells (engrafted cells) attacking your body, or about getting a new infection from another person. But there can still be graft failure, which means the cells don’t go into the bone marrow and make blood cells like they should. A disadvantage of an autologous transplant is that cancer cells may be collected along with the stem cells, and later put back into your body. Another disadvantage is that your immune system is still the same as it was before the transplant. As the cancer cells were able to escape attack from your immune system before, they may be able to do so again. To help prevent this, some places treat the stem cells before giving them back to the patient to try to kill any remaining cancer cells- this is called purging. Again, this has problems because some normal stem cells can be lost during this process. This may cause your body to take longer to start making normal blood cells, and you might have very low and unsafe levels of white blood cells or platelets for a longer time, increasing risk of infections or bleeding problems.
 
Allogeneic stem cell transplants are when the stem cells come from a matched related or unrelated donor. In the most common type of allogeneic transplant, the stem cells come from a donor whose tissue type closely matches the patient’s. Blood taken from the placenta and umbilical cord of new-borns is a newer source of stem cells for allogeneic transplant. Called cord blood, this small volume of blood has a high number of stem cells that tend to multiply quickly. But the small volume normally does not contain enough stem cells for large adults, so is mostly used for children and smaller adults. A positive to this type of stem cell treatment is that the donor stem cells make their own immune cells, which could help kill any cancer cells that remain after high-dose treatment. This is called the graft-versus-cancer effect. Also, the donor can often be asked to donate more stem cells or even white blood cells if needed, and stem cells from healthy donors are cancer-free. Cons- the transplant might not take; the transplanted donor stem cells could die or be destroyed by the patient’s body before settling in the bone marrow. Also, the immune cells from the donor may not just attack the cancer cells- they could attack healthy cells in the patient’s body. This is called the graft-versus-host disease. There is also a very small risk of certain infections from the donor cells, but as donors are tested before they donate, this is rare. A higher risk comes from infections you had previously, and which your immune system has had under control. These infections may surface after allogeneic transplant because your immune system is suppressed by medicines called immunosuppressive drugs. Such infections could cause serious problems, if not death. 
 
Of course, this all brings up the question of why can we not use stem cell transplants to cure all HIV patients? The answer is that it would not be possible to find enough genetically matched bone marrow donors with the naturally occurring genetic mutation to treat the 33 million people with HIV, even if that was desirable, safe and ethical. Also, most people with HIV already have very compromised immune systems, and so carrying out stem cell transplants would carry a significant risk, which may not be outweighed by the benefits.   
 
GENE THERAPY:
 
A lot of research has gone into the potential of using gene therapy for treating and preventing diseases in general, and specifically for HIV. Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. There is research into several approaches to gene therapy, including:
- Replacing a mutated gene that causes disease with a healthy copy of the gene.
- Inactivating, or ‘knocking out’ a mutated gene that is functioning improperly and causing unwanted consequences.
- Introducing a new gene into the body to help fight a disease.
Gene therapy is a promising treatment option for a number of diseases, including inherited genetic disorders, some types of cancer, and certain viral infections. However, the technique is risky and is still under study to make sure that it will be safe and effective. Gene therapy is currently being tested only for diseases that have no other cures.

Gene therapy is promising in helping cure HIV because people who are naturally resistant to HIV have two copies of the CCR5 receptor due to a random mutation. Gene therapy could be used to give people the second mutated copy of this receptor if they target the CCR5 receptor, hence, curing people of HIV. However, gene therapy is still a controversial technique, and whilst many believe that it will become a staple of 21st century medicine, experts say society will be better served if medical researchers proceed slowly and prudently. Therefore, it is likely to be decades until gene therapy becomes normalised in modern medicine. And for specific treatments, such as this supposed HIV cure, many years of testing, clinical trials and waiting for approval would have to pass before the treatment becomes available.

CN: picture of brain surgery

​How do brain tumours form?
A brain tumour occurs when brain cells divide and grow in an abnormal and uncontrolled way. When a cell divides, it copies its genes and replicates itself. Sometimes however, mistakes occur in this process, and are known as mutations. Whilst some mutations are harmless, others cause the cell to divide uncontrollably.
 
The mutation causes the cells to behave as though they are receiving a growth signal or deactivates the checkpoints that would stop the cells from dividing. Therefore, the cells continue to divide uncontrollably, forming a tumour

​What is glioblastoma?
 
Glioblastomas are the most common and aggressive type of brain cancer that forms from cells called astrocytes in the nervous system. They belong to a group of brain tumours called gliomas, which are malignant tumours of the glial tissue. The average age of patients with glioblastoma is 64 years old; its risk increases with age. Whilst glioblastomas are mostly found in the cerebral hemispheres, they can be found anywhere in the brain.
Glioblastoma is a ‘diffuse’ tumour, meaning they are infiltrate and able to spread into healthy tissue in other parts of the brain, and therefore is very fast growing and fast spreading. This makes it very difficult to pinpoint precisely where the tumour starts and ends. Particularly aggressive glioblastoma are able to even spread to the opposite side of the brain through connection fibres, known as corpus callosum. Gliobastoma’s ‘diffuse’ property is particularly problematic when tumours spread near to important regions of the brain that are essential to functions such as movement and coordination.

​Symptoms and side effects of glioblastoma
Due to mass swelling from the fluid surrounding the glioblastoma (edema), patients develop symptoms very quickly. The most common symptoms are nausea, vomiting and severe headaches, and are predominantly due to the increased pressure in the brain as a result of the tumour and swelling. Neurological symptoms are also not uncommon, for example, weakness, sensory changes, difficulties with balance, and neurocognitive or memory issues.
 
Treatment of glioblastoma
Mark Gilbert, director of the Neuro-Oncology Branch in NCI’S Centre for Cancer Research said, “Glioblastoma is one of the hardest to treat in the history of oncology.” Despite continued efforts to develop promising treatments for glioblastoma, none have proved successful, with only 3.3% of patients living for longer than 2 years. The usual treatment for patients with glioblastoma is a surgery to remove most of the tumour, followed by chemotherapy and radiation.

​Surgery
Commonly, surgery would take place in an attempt to remove as much of the tumour as possible- a procedure known as debulking. It is difficult to remove the entire tumour because glioblastoma is a diffuse tumour, which means it can spread into the rest of the unaffected brain, and so it is difficult to tell the difference between affected and unaffected brain tissue.
There have been recent advances, which have improved the extent to which the tumours  can be removed in surgery. Prior to surgery, patients are given a drink containing the substance 5-ALA, which causes the affected cells to glow pink under violet light. This makes it less difficult to tell the affected and unaffected cells apart, and so more of the tumour can be removed.
Surgery is also used for palliative treatment in cases where the tumour cannot be removed- intracranial pressure is reduced to relieve symptoms.
 
Radiation
Radiation involves the use of high precision high-energy beams, for example X-rays, gamma rays or protons, to kill the affected cancer cells.  An immobilization mask is worn by the patient to hold their head in the same position and limit movement. Intensity-modulated radiation therapy is an advanced mode of radiotherapy that uses computer-controlled liner accelerators to deliver precise radiation doses to a malignant tumour. It allows for the radiation dose to conform more precisely to the 3D shape of the tumour by controlling the intensity of the beam in small volumes. The treatment is planned specific to the tumour using the CT and MRI images of the tumour in conjunction with computerized dose calculations to determine the dose intensity pattern that is best suited for the tumour.

​Chemotherapy
Chemotherapy is a technique that uses cytotoxic drugs to kill the affected cancer cells. Temozolomide, Iomustine and carmustine are the most commonly used drugs in chemotherapy. Temozolomide works by preventing the tumour cells from making new DNA, which prevents them from making new cells and therefore growing. It also makes the affected cells more sensitive to radiation, so chemotherapy and radiation treatments are often used together. Whilst radiation acts on the affected tumour cells, chemotherapy acts on all dividing cells, but healthy cells are able to repair themselves easier than the tumour cells, so few healthy cells die after treatment. The various ways in which chemotherapy can be given are:
 
Tablets- chemotherapy drugs can be taken in tablet form and are absorbed and carried around the body in the bloodstream to reach the affected tumour cells.
Injection/drip- chemotherapy drugs can be injected into a vein or into the spinal fluid. A drip may be used to insert the drug into the bloodstream, where it is absorbed and carried around the body to the affected cells.
Wafers- drugs can be put inside a polymer wafer and inserted into the brain during surgery. The wafers are made of a biodegradable material so they can dissolve over a few weeks, releasing the drug into the brain to kill the tumour cells.
 
Immunotherapy-Vaccinations
Whilst several immunotherapy-based treatments have proved unsuccessful in facing glioblastoma, vaccinations has been considered to be one of the more promising approaches.
A particular advance in the use of vaccines for glioblastoma was made by Dr Jason Adhikaree from the University of Nottingham, who proposes to use dendritic cells, a type of white blood cell, to create the vaccine. The dendritic cells would be taken from the patient’s body and ‘taught’ to recognise and kill the glioblastoma-affected cells. They will then be injected back into the patient’s body, in which they can attack the tumour cells.

By Maheria Rashid