Finding A Curative And Preventive Basis For Mental Illness.

Mentally ill people need help not stigma
Image credit to Imagebuddy

I just finished a 4-week rotation through Psychiatry, and I must say I have learnt a lot about the disorders of the mind. Before the rotation, I used to have this stigma and nausea towards anything that has to do with mental illness and those with it because of the way the society has painted them--they are mad people. But the truth is people with illness of the mind are normal human beings with families, friends, dreams and ambitions; some have good education and are in different professions. Our first lecture introduced us to Psychiatry, and in it I learnt that everyone's mind is like an elastic spring suspended from a hook, with a board on one end. Now, life drops different loads on this board (what we call psychological stressors--challenges and trials), which stretch the elastic spring (remember Hooke's Law in Physics); but almost all the time, our minds will return to their original length after a "normal brief period" of reacting to the stretching (in the form of crying, sadness, feeling depressed, losing interest in everything, fear and anxiety, and so on) when we've got over the psychological stressors (every challenging period passes). It's important to note that some people's minds have higher elastic limits than others' (they can withstand much more severe psychological stressors than others) because of their genetic makeup. Hence, when those whose minds have low threshold for withstanding challenges are faced with very severe psychological stressors, their minds are stretched beyond their elastic limits and what results is mental illness--a state in which their minds remains in this stretched mode for an unusual length of time, in the form of depression, mania, obsession, hallucinations, compulsion, changes in personality and so on. 

This Technology Could Solve the Climate Change Problem by Generating Low-Carbon Fuels from Sunlight.

Carbon Emission at the heart of  Climate Change.
Image Credit to GeekSnack

Like it or not, most of the world people depends on crude oil and its products and other heavy carbon-emitting fossil fuels such as coal for one of the most important needs in life-energy (from petrol and diesel for cars and other vehicles through gas for power plants to generate electricity for cities to other fuel products used in many other dimensions). Every day hundreds of millions of litres of gas and other related fuels are burnt in one way or the other to meet this basic need for energy. While the basic need, energy, is being met, the basic need of our environment -including the atmosphere of which the ozone layer is part; the water bodies; and the green lands--which demands moderate waste output from us, that is within its recycling capacity, were neglected from the very beginning.

However, the world started to realise the consequences of this neglect and efforts to make amends went into motion. That was when global consolidations to tackle the problem of climate change began to take shape in various parts of the world and from various strata of the society--from the political line, through various social groups to the academia and various research and development industry groups. Significant progress began to materialise in the form of environment-conscious government policies; a change of attitude towards energy use by people in various parts of the world; and technological adventures and innovations and inventions from the academia and research and development industry groups. We began to hear about less carbon-emitting fuel alternatives such as biomass fuel; then came the green energy in the form solar electricity that emitted zero carbon into the atmosphere. These breakthroughs found their way into the various purposes that were being served by the heavy carbon-emitting fossil fuels and the result was solar powered homes and communities; electric cars and trains and power plants that generate electricity with biomass fuel.

Even with all this, the dependence on fossil fuels did not witness a marginal decline. But the need to meet the need of the environment began to experience unprecedented surge. Global conferences by the world's political representatives on addressing climate change issues became almost an annual mandate. However, the truth is that the fossil fuel industry is a multi-billion, if not multi-trillion, dollar one; and a complete shift from it to green energy will be almost impossible (though there are already campaigns going on in several UK Universities and institutions for divestment from future fossil fuel), the least reason being that most of the green energy alternatives have limitations such as low conversion ratio and low carrying capacity--conversion of solar energy into electrical energy is at a less than 2% rate and I'm yet to learn of a solar powered heavy machinery factory. And secondly, countries like the US and Russia are ever expanding their technologies in exploring shale gas from rocks and natural gas in the Arctic region of the planet respectively, never minding the fact that about 80% of the remaining coal reserves, 50% of gas and 30% oil must remain unburnt if the world is to remain below the 2ºC global warming beyond which catastrophes may start manifesting.

Find Out How This Technology Takes People's Facial Pictures Without Seeing Them

Hello my friends the world over; I know I have been unbearably absent (for almost six months now) and I'm truly sorry for that, though the reason was beyond my control (I have been preoccupied with attending to my foremost duties, encompassed in Med School). However, I'm back here for you, though I can't promise to be regular because I don't make promises and fail to keep them. To begin with my resumption, do you think it's possible to create a 3-D image of your face without seeing you (to either draw you or take a shot with my camera)? Well, it could have been described as magic in the 1980s, but the capability of our human mind is limitless and its manifestation in science and technology pushes boundaries further every day, and below is just a demonstration of that boundary pushing. Enjoy

I read the story of a man in the US who was charged with rape and murder, and jailed for over 35 years back in the early 1980s, but by 2011 he was released from prison after concrete evidence emerged that he didn’t commit the crime and that the real offender was finally apprehended after matching the DNA samples collected from the crime scene back in the 80s. I was furious after reading the story and wondered what limitations in the investigation could have led to wasting 30 precious years of an innocent man’s life. But it happened that after running the DNA samples obtained at the crime scene  through the FBI crime databases containing DNA and fingerprints of convicts and previously arrested suspects, and after comparing with DNA samples of suspects arrested after the crime, there was no single match because the culprit was a first time offender who went on the run; and this man who ranked higher among the arrested suspects ended up in jail: and I’m sure many people are serving jail term out of similar situations.

Snapshot. Image credit to Parabon NanoLabs

This was a very helpless situation for the man; but such state of helplessness could become a thing of the past, like the time period called 1980s, with the work of a company called Parabon NanoLabs in Columbia, US because it shares my concerns for such terrible setbacks to forensic crime investigations. By leveraging the unlimited potentials of the Human Genome Project and harnessing the power of modern genomic sequencing, scientists and tech experts at Parabon NanoLabs have developed a technology they call Snapshot that can construct a 3-D facial image of any person with DNA samples from them. Let’s say it’s a tech form of genotype to phenotype translation we’ve been taught in Biology, Physiology and so on. But Snapshot creates these facial images by scanning and interpreting genotype data sets (several groups of unique DNA sequences called short nucleotide polymorphisms), input into it from any genome, which are very strongly linked to phenotype data sets such as pigmentation (eye, hair and skin

colours); the shape of your nose and mouth, and other facial morphological features; presence of skin spots; ancestry and other features that distinguish one person from another.

To further strengthen the reliability of this technology, DNA samples from convicted criminals have been used construct their facial images from Snapshot and then compared with their photographed images, with greater than 80% accuracy in features like pigmentation and ancestry; features like presence of skin spots scored below 50% due to inclusion of DNA sequences that express more than one feature, and the guys at Parabon are working to eliminate this ambiguous sequences and scale down to only ones that are unique to specific features in very closely related people like those from the same family.

In addition, I did watch a few episodes of Criminal Minds, a TV series where FBI Behaviour Analysts create psychosocial profiles of suspects from the patterns and nature of crimes at crime scenes; even if a bit of this is done in real life, it’s still based on the database of arrested suspects and convicts whose psychosocial statuses have been profiled and whose crimes are well documented. But what happens when a serial killer, who has never been suspected and arrested before, doubles as a very smart chess player and commits his crimes based on moves (I learnt there are millions, if not billions, of possibilities for the first four moves on chess)? Definitely, Criminal Minds will remain behind TV screens unless investigation agencies have the time, resources and manpower to bring over a million Behaviour Analysts to such crime scenes. However, with this novel technology called Snapshot, such suspects can’t play chess with their DNA sequences; and if it is combined with Criminal Mind-like investigations, crime investigators will certainly make definitive criminal diagnosis for almost every case so that innocent people, like the US man I read about, wouldn’t have their life years taken from them. 

Finally, this Snapshot technology seems to fundamentally focus on the crime investigations sector; but I think so many other sectors can benefit immensely from this technology. Feel free to exercise your imaginative rights and comment on further present and future applications of the technology. Thank you.

I wrote this piece primarily for the June edition of Klatsch Magazine run by Just4meds, a social media site for people in the medical profession--from medical students and students in other allied medical fields to consultants in these medical fields--to interact with each other anywhere in the world. Just4meds was founded and is run by a classmate of mine at the College of Medicine, University of Ibadan and the University College Hospital, Ibadan, Nigeria.

Can this Treatment Empower the Body's Immune System to Root out Cancer?

I saw a patient in early 2013 when I did my first rotation in Surgery. She had breast cancer and after

Breast Cancer Undergoing Programmed Cell Death.
Image credit to Wellcome Trust UK

undergoing what we call a modified radical mastectomy (surgery which involves removing almost all the breast tissue), she died a few days later. Why? The breast cancer had spread a bit to other parts of her body before the surgery; and unfortunately, CT scan of the brain was not done to check whether it was safe before taking her into the operating theatre. And surgery usually suppresses the immune system and in this woman's case it gave room for the already spreading breast cancer to become very aggressive in invading other parts of her body, most painfully including her brain. She started having seizures a day after the surgery and died three days later.

Cancer is one of the leading causes of death in the world: it has robbed many families and friends of their loved ones; it has withered the blossoming dreams of many people.

A Cell from Malignant Skin Cancer (Melanoma).
Image credit to Wellcome Trust UK

Mankind has long been in the battle against cancer with moderate victory-the disease has had much of the victory. And the most common treatment modalities (such as chemotherapy, radiotherapy) available against the disease have untold consequences which sometimes outweigh the benefits; consequences manifesting in the form of adverse effects such as hair loss, skin wrinkling, suppression of the immune system, predisposing the patient to infection, and so on, because these treatment modalities also destroy normal healthy cells and tissues in their course of weeding out the cancerous cells. Removal by surgery is another treatment option whose success largely depends on the time of diagnosis of the cancer: when discovered very early, surgery is likely to open a huge window of extended lifespan (not cure because the cancer may show up again after some years); but if the cancer is diagnosed late, surgery can't do anything because some prodigal cancerous cells would have defied their parent tumour and migrated to very distant and, often dangerous, locations such as the brain, lungs, liver and so on.

Nevertheless, there have been significant efforts and dotted success in the quest to find lasting treatments for cancer in the past 50 years. However, to speak of a cure for a particular type of cancer in its advanced stage, when the possibility of its metastasis (spread to other tissues and organs in the body is very very high), is something that cancer treatment experts at the patient's bedside will meddle in with utmost caution.

But it seems that the phrase "cure for cancer" may just begin to crawl into the vocabulary of cancer treatment in the very near future as insinuated by a research published in the journal Nature on the 27th November, 2014, which details the trial of a new drug class called immune checkpoint inhibitors (belonging to a type of cancer treatment modality called immunotherapy) in patients with late-stage cancer of the bladder and whom doctors have given a maximum of eight months to live. Greater than 50% of the patients enrolled in the trial started recovering after taking the drugs, while two patients out of the total number seemed to have been cured after receiving the treatment as there were no signs of cancer in them. In the patients who responded to the treatment it was found that their own bladder cancer had cells which express a molecule called Programmed Death Ligand (PD-L1) on their surfaces.

Cell Division in a Skin Cancer Cell.
Image credit to Wellcome Trust UK

Immunotherapy is a treatment modality for cancer that aims to help the body's immune system fight these cancers. An aspect entails tweaking the main cells involved in fighting cancer (we call them T cells) genetically to be able to fish out these tumours much more effectively; while another uses a type of chemical interleukin-2 to speed up the immune system's anger towards these cancers, a modality pioneered by scientists at the US National Cancer Institute in 1985 and which was used to cure some patients with melanoma (malignant tumour of the skin). These subforms of immunotherapy have not had the overwhelming success scientists envisaged them to record; but perhaps this new subform called Checkpoint Inhibition therapy may finally fulfil the omnipotence prophecy against cancer being alluded to immunotherapy.

The concept of immune checkpoint inhibition arose when scientists discovered that one of the chemicals, called interferon gamma, released by the T cells fighting cancers made the cancer cells to adapt to the assault of the immune system by developing a molecule called Programmed Death Ligand. Programmed Death Ligand binds to a receptor molecule on the surface of T cells called Programmed Death receptor; this receptor is probably involved in moderating the rage of the immune system cells in their fight against foreign entities that invade our body so that the immune system doesn't go mad and destroy normal healthy cells and tissues in their anger at the foreign agents; and they possibly do this by binding with Programmed Death Ligang-like molecules that are released during inflammatory processes; hence the programmed death ligands and receptors serve as checkpoints of the immune system in the time of war. But cancer, being a smart player in the survival of the fittest, decided to leverage on this cloaking spell. Hence, when T cells infiltrate these cancers and release interferon gamma and other chemicals that signal the rest of the immune system to attack, the cancers release the Programmed Death Ligand to bind the Programmed Death receptors on the surfaces of the T cells, making them think they are about to go crazy in this their fight to liberate our body and leading to the T cells taking their feet off the accelerator: the smart cancer laughs and continues growing.

But cancers aren't smarter than us; in the mid-90s scientists started working on molecules that could block the Programmed Death receptors on the surfaces of T cells and the Programmed Death Ligand produced by the cancer cells in patients so that the immune system will unleash its full wrath on the cancer cells. By 2012 clinical trials have already gone far in the US and some European countries to test a few monoclonal antibodies (drugs that are made by artificially synthesizing antibodies in the lab specific to particular protein fragments in disease antigens, unique protein molecules expressed by different cells-both healthy and diseased ones depending on the choice of a researcher) that have been developed specifically against the PD-1 receptor molecule on the surface of T cells and the PD-L1 molecules produced by cancer cells. The results of the clinical trials have produced spikes of miracles as some of the patients with late-stage cancers (with the cancer having spread to other parts of the body) witnessed their malignant tumours regress very significantly, and some tumours were even totally wiped out, including their colonies in different parts of the body (the lungs and liver where the tumour has spread to were found clean after rounds of cancer-detecting investigations). The development and success of these drugs (monoclonal antibodies) called immune checkpoint inhibitors were heralded as the most significant scientific breakthrough of 2013 by Science Magazine.

While almost half of those that enrolled in the various clinical trials for the immune checkpoint inhibitors seemed to have benefited from the drugs, the remaining half have not responded to the treatment probably because, as some cancer immunologists pointed out, their own cancers might be using a different pathway to leverage on the immune system checkpoint. And I think the way forward in this immune checkpoint inhibition modality is to now look at the genetic basis of the synthesis of programmed death ligand-like molecules in cancers. This may reveal, I believe, rate-limiting steps either at the messenger RNA transcription and translation levels and post-translational modification levels that may be totally different from those of other inflammatory processes in the body in which the immune system checkpoint may be very crucial to preventing autoimmune reactions; it may also throw light to polymorphisms unique to the genes encoding programmed death ligand-like molecules in cancers. Success in this direction will provide a wide range of targets for drug development that will benefit virtually every cancer patient because each group of drugs will target unique points that may be the engine room for a small group of cancer patients (pharmacogenomics and personalised medicine). One feasible way this 'way forward' could be achieved is incorporating this proposal into research initiatives such as the International Cancer Genome Consortium, the UK Cancer Genome Project and the US Cancer Genome Atlas  working to identify the genes involved in cancer development in thousands of patients (and I want to believe that cancer researchers have already thought about this and are moving in that direction); another way is to use animal models to induce cancers and then study the genesis of leverage of the immune checkpoint by the cancer cells right from the genetic level.

I believe we will keep gaining more grounds in the fight against cancer through the development of several weapons to destroy it from virtually every angle; a few weeks ago, Cambridge University reported the approval by the European Union drug regulatory body of a new generation anti-cancer drug developed by its scientists in collaboration with the biopharmaceutical giant, AstraZeneca. The drug called Lynparza exploits a totally different pathway to fight cancer: it inhibits an enzyme called PARP (Poly ADP-Ribose Polymerase) involved in a pathway for the repair of damaged DNA in replicating cells; and its efficacy lies in the fact that some malignant tumours have only this pathway for repairing damages to DNA unlike normal healthy cells that have alternative repair mechanisms such as the homologous recombination pathway. Lynparza has been licensed for use in patients with advanced ovarian cancer (with mutations in two genes called BRCA1 and BRCA2 which are involved in ensuring repair of sustained damages to DNA in healthy cells through the homologous recombination repair mechanism) in Europe; clinical trials have shown Lynparza to have very minimal side effects compared to other chemotherapeutic agents because of its specificity in targeting only cancerous cells; and since some other cancers (breast and pancreatic cancers) have mutations in the BRCA1 and BRCA2 genes, they are potential therapeutic targets for Lynparza.

This new year and the years to come definitely will see us winning most of the war against cancer.