I must have the "Call of Duty" gene.

Is there a gene for loving Call of Duty?

Genes are brilliant; and yet the way they are depicted may seem to oversimplify some really complex issues.

If you watched BBC’s Horizon last week, entitled “Are you good or evil” you would have been entertained with the idea that scientists have uncovered the genetic basis of being evil. The “warrior gene” as it has been dubbed is thought to induce aggressive behaviour after provocation. In the documentary they showed a case where a man murdered his wife, but avoided a conviction for first degree murder, because scientists measured the expression of the “warrior gene” which convinced the jury that an underlying genetic trait was to blame for his actions………….I know.

If you also picked up the Metro on the 6th September (every Londoner does), you would have caught the following headline:  “Lazy people are missing athletic gene according to new study”. This gene called the “exercise” gene is believed to be deficient in couch-potatoes. The research was actually carried out in mice and the scientists demonstrated by deleting the “exercise” gene, that these mice were less active compared to their wild-type (normal – undeleted) counterparts. The gene actually encodes for an enzyme called AMP-activated protein kinase and it is a fundamental enzyme involved in metabolism, homeostasis and with glucose uptake in muscle tissues as a result of muscular contraction. Whilst it is an interesting find to demonstrate the physiological impact in mice, it might be stretching it slightly to say that it is “the” exercise gene.

Of course, our love for genes doesn’t end there, one post in a lifestyle feature describes – the “happy” gene. You guessed it, it is the gene that determines whether or not you have a bounce in your walk and see the glass as half full rather than half empty. I relish the fact that its called the “happy” gene because scientists actually called the gene 5-HTTLPR. This gene encodes for a serotonin transporter, which is a neurotransmitter (a brain chemical) that has been shown to influence mood and happiness. So albeit slightly indirectly 5-HTTLPR is believed to play a role, by affecting the transport of serotonin. One of the comments on this article is slightly amusing but also raises an important question.

tspears0901 says ” I dont care which ” gene ” anyone has, if life is tough, it makes you depressed, end of.”

“The relationship is rarely one to one.”

You see after reading these articles, I feel slightly sorry for genes. It is almost as if every single gene must have a really important purpose. The fact of the matter is, one gene does not control complex outcomes like being evil, lazy or happy. The relationship is rarely one gene to one outcome and thats without weighing in the other important factors such as nurture. So how do you even begin to unravel the importance of multiple genes at the same time and see if it can lead to complex issue? One method is by conducting gene expression profiling experiments. So taking our case of understanding the genetic basis of being “evil” you would take a group of psychotic people and then sample lots and lots of genes with the hope that you’ll identify a group of genes that you think might be important in psychosis, because it is either up or down regulated (expressed highly or less). You’ll then compare those same genes against a group of people that are not psychotic to truly identify if these genes are important, this is called your control sample. The output of such an experiment will form a genetic “profile” which, is more reliable as a measurement because you’re not just measuring one gene; it also provides a sort of genetic signature or fingerprint for that particular physical state, in this case, psychosis.

Another important aspect to consider is the functional relationships between genes. In an article published in Nature, Dr. Heather J Cordell discusses how gene-gene interactions are important in understanding human disease (link provided at the end). She states, “If a genetic factor functions primarily through a complex mechanism that involves, multiple other genes and, possibly, environmental factors, the effect might be missed if [one] gene is examined in isolation…” The crucial point here is that analysis of a gene in isolation is probably giving you an incomplete picture. Dr. Cordell then continues to describe some of the mathematical models that are used to determine working relationships between genes and this is because more often than not, it is many genes working together that leads to outcome – not just one.

“Take the word “competitive” and imagine that it is a gene.”

Some genes at this moment in time simply have no purpose, we haven’t figured out what every single gene does and it is one of the reasons why we have lots of genome projects currently engaged. One example is the “The 1000 Genomes Project” which is sequencing the DNA from a large group of people from different ethnic backgrounds. This experiment aims to identify our genetic differences and determine if such differences give rise to specific disease states. This is because for a specific gene, there can be variations in the underlying DNA sequence in specific groups (such as ethnicity) of people and as a result the functional consequences might be differ too. One way to think of it, is to consider a thesaurus. Take the word “competitive” and imagine that it is a gene. If you look up the word in a thesaurus you’ll get the following words, “ambitious”, “aggressive” and “keen”. You could in a sentence replace the word “competitive” with any of the three that I have mentioned, but it wouldn’t really give you the same meaning.

My friend Sunniyat, he is so competitive. vs. My friend Sunniyat he is so aggressive. 

Genes are similar. There are slight variations of the same gene that can have different functional consequences. Its called a genetic polymorphism. So take the “happy” gene for example, it actually may not be the secret to happiness for all of us because of our individual genetic interpretations of a single gene.

“DNA doesn’t all code for genes”

Genes are not the only functional aspect of our DNA. It may seem a little strange, but DNA doesn’t all code for genes. This is a little difficult to explain, so forgive me if this example fails to work. Imagine opening up a story book (yes another literary based analogy) and you start reading it, but it looks like this :

“dfasdOncesdfauponadaadfastimeasdas”

Imagine each word that you see in that quote is a gene, something that has a meaning and function. Our DNA is also like the above, full of lots of code that we don’t quite understand yet. The ENCODE genome project is attempting to characterise what all the code in between the genes actually do. This is called “non-coding DNA” because these sequences don’t code for genes, but just because they don’t encode for genes and they harbour an apparent lack of function, doesn’t make these sequences less important. In actual fact over 90% of our DNA is non-coding and to assume that 90% of our DNA has no functional consequence would be wrong.

“The thing about scientific research is that it is a field that builds upon current knowledge”

I don’t think scientists or science journalists are to blame here. The thing about scientific research is that it is a field that builds upon current knowledge. Hence incremental progress is reported in the papers usually with an exciting sweeping headline (ahem…) So the next time you come across an article where it describes a single gene, and how novel research has correlated it to single outcome, whether that be a disease state, behavioural outcome or physical characteristic just remember that its probably a little more complicated than that. And no, sadly there isn’t one gene for loving Call of Duty, but there might be a few!

 

References:

Evil gene: http://www.bbc.co.uk/programmes/b006mgxf

Exercise or Lazy Gene (depending on which way you want to look at it): http://www.metro.co.uk/news/874579-lazy-people-are-missing-athletic-gene-according-to-new-study

Happy Gene: http://lifestyle.aol.co.uk/2011/09/10/have-you-got-the-happy-gene/

Gene-gene interactions: http://www.nature.com/nrg/journal/v10/n6/abs/nrg2579.html

Both scientists and members of the public alike can relate to the determination of this billboard.

Cancer: Why we don’t have a cure just yet.

To say that cancer is a complex disease to understand and a difficult disease to treat would be a great understatement. Those that have lost loved ones to cancer describe the experience as a long and torturous path, full of deception. At times those diagnosed with cancer seem as though they have their energy back, eating food and sharing moments with close family members in a growing air of optimism, which is then subdued by unpredictable crashes of ill-health. What is certain however is that the experience is not the same for everyone. My own mother-in-law passed away from cancer sadly before my wife and I got married. Seeing my wife grieve was difficult because I felt very helpless. I was studying at the time and in fact, I contribute the direction that my life is heading now to that moment in time.

I work in the exciting field of cancer research. I’m fairly low in the academic hierarchy (as a first-year PhD student), but what I lack in experience, I make up in enthusiasm and of course, one of the most frequent questions that is asked of me by my friends and family is whether or not we are closer to finding a “cure”. I usually try to provide some sort of answer, but if I am honest with myself it is rarely clear enough for everyone to understand. So this time lets start from the very beginning.

“To understand cancer, you have to come to terms with a shocking fact.”

With cancer the relationship status is “complicated”. Our body is made up of trillions of cells. Each cell has a particular identity and purpose both of which are programmed by genes coded by DNA. These genes are turned “on” and “off” at different rates and for changeable durations during the lifetime of that cell. You may without realising tried to imagine this like a light switch; instead a better way to consider it is like a dimmer switch. The output in this case is the great macromolecules called proteins. So DNA is the language that describes the genes, whilst the genes encode for proteins, this is often referred to as the central dogma of molecular biology. The proteins are the hard-working molecules in the cells that have a specific function. Some of them provide structural support, others are involved in elegant processes such as DNA replication whilst some proteins have crucial enzymatic activity to allow them to control cellular metabolism and to pass information from outside of the cell to the inside of the cell. As you can imagine, the inside of a cell is a busy place and in amongst this chaos there is a delicate balance keeping that cell alive.

To really understand what cancer is, you have to come to terms with a shocking fact. Your cells are constantly thinking of suicide. It’s called programmed cell death or if you prefer the buzzword, its called apoptosis. For cells to continue to grow and divide they need to respond to growth signals which allow them to progress through the cell cycle. The cell cycle is composed of periods of growth, replication (mitosis) and resting. Crucially, cells are not supposed to go through this cell cycle without regulation. So there are molecules that create checkpoints, that ensure that cells are progressing through this cycle correctly. Occasionally this cycle becomes entirely unregulated, allowing the cells to grow uncontrollably. If this happens, apoptosis kicks in and the cell decides to kill itself rather than going on an endless cycle of proliferation. It is a noble act, cells killing themselves to ensure the survival of the whole organism, and yet cancerous cells are far from noble. Some cancer cells are able to turn off the process of apoptosis entirely, but it doesn’t stop there. They are also able to evade cell cycle checkpoints giving them a clear path to continue replicating, growing and dividing. What started off as a humble, single cell soon turns into a tumour (a group of cancerous cells). This is what cancer is. It is a disease that starts from one cell before becoming many damaging cells.

“The vast majority of cancers are sporadic.”

Scientists have been working hard to understand the origins of cancer. At the most basic level, cancers arise as a result of one cell gaining a genetic mutation. This is where the DNA in the nucleus of the cell becomes damaged, particularly the parts of the DNA that encode for a gene. If it affects the genes then you might be thinking that cancers are always inherited, this is actually not true and in fact only 5-10% of cancers show strong dominant mode of inheritance, whilst 10-15% show a relatively weak correlation and may require additional environmental factors leading to the onset of cancer. Sadly, the vast majority of cancers are sporadic. This makes it incredibly difficult to determine who will and who won’t get cancer.

Having said that, scientists have attempted to characterise both the genetic and the non-genetic risk factors for some of the cancers. A genetic risk factor, is where a mutation (DNA damage) in a specific gene results in an elevated incidence of cancer. For breast cancers, a genetic risk factor includes mutations in the BRCA1 and BRCA2 genes. These genes are called tumour suppressors, because when these genes are turned “on”, the resulting protein stop uncontrolled cell growth – hence the term suppressor. When the gene is mutated the protein that the gene codes for doesn’t work properly and the important function it could once do is lost. A non-genetic risk factor is relatively easier to understand, such as smoking. Smoking is so clearly correlated to lung cancers, there has been significant effort made to ensure smokers are aware of the said risks. Characterisation of these genetic and non-genetic risk factors take considerable time, but that hasn’t stopped some scientists. The Sanger Institute in Cambridge is currently embarking on the Cancer Genome Project which is trying to identify the genes that are mutated in cancers, particularly the ones that arise as a result of sporadic mutations. It is believed that this study will be able to identify a list of genes that play a significant role in cancer progression and allow for the development of focused therapies. Identification of the non-genetic risk factors is in contrast less focused, with numourous research groups working on the issue by attempting to understand the environmental background of people that get cancer. Some of these examples include levels of exercise, diet, viral and bacterial infections, alcohol abuse and so on. These are believed to be factors that you can control and unlike your genetic make-up, which cannot change after birth, health professionals can instead help you make behavioural decisions to prevent the onset of cancer. One more reason to eat your 5-a-day!

“The most profound issue is specificity.”

What about therapies, what is the biggest challenge? Trying to remove cancerous cells from your body is like trying to do something very precise with an extremely blunt and large object. The most profound issue is specificity. When people think of cancer treatments, more often than not, they think of chemotherapy; a mixture of drugs taken to kill the cancer cells. However, ensuring that the drugs only target the cancerous cells is substantial challenege. One of the physical characteristics of cancer cells is their ability to divide rapidly and continue growing at a faster rate than healthy cells. As a result many drugs attempt to inhibit the DNA replication machinery in these cells, as cells need to replicate their DNA to continue dividing. These therapies are non-specific and healthy cells that also grow fairly rapidly are affected by the treatment. One such example are the white blood cells that are fundamental in mounting an immune response against bacteria and viruses. So whilst the chemotherapy may have an opportunity to kill the cancerous cells, the cancer patient is likely to become immunocompromised after sustained chemotherapy, it can lead to the increased risk of patient suffering from opportunistic infections. All is not lost though. Novel treatments include targeted therapies by using antibodies to deliver a payload of cytotoxic (cell killing) drugs. Antibodies are molecules that are able to specifically bind to bacteria and viruses allowing your white blood cells to find them and destroy them. Rituximab is an example of a chimeric antibody which is able to bind to cancerous white blood cells and initiating apoptosis. Such targeted therapies are an important focal point for cancer research and continues to be a promising avenue of research.

“We are steadily winning the battle against cancer.”

Cancer researchers are one of the most determined bunch of scientists I have ever met. They often work deep into their week nights and over their weekends. Although scientists have yet to find a “cure” for cancer, there is hope knowing that we are steadily winning the battle against cancer. The below chart shows how over the last 30-years the survival rates for breast cancer have increased, which is a great achievement against one of toughest medical challenges faced by modern day humans. What is certain though, as per the billboard by the Leukaemia Research Fund, is that scientists won’t hang up their coats until the job is done.

Breast Cancer Survival Rates, Cancer Research UK.