Genomic Enterprise Blog

Cancer is a disease of the cells. The body is made up of a community of individual cells, each of which has a specific job to ensure that the community functions correctly. Liver cells must detoxify the fluids of the body, lung cells must exchange oxygen and carbon dioxide from the blood, and skin cells must separate the outside world from the inside of our body. In addition to performing their assigned jobs, cells are also good citizens. Cells respect the space of the other cells around them and support the healthiness of those cells. Occasionally, cells begin to grow in an uncontrolled fashion, causing many problems for the body. Cancer is a disease of uncontrolled cell growth or proliferation. Cancer cells are no longer good citizens. For instance, a liver cell that becomes cancerous no longer does its job of detoxifying the body. In addition, cancer cells do not respect their neighboring cells and will crowd them out of existence. We always had this concept that is still used in pathology today that each cancer type refers to the tissue and cell type of origin. In that case, breast cancers would emerge from the breast cells and have their original characteristics. It turns out that cancer is a combination of many different diseases in one. Cancer is not a single disease, but literally hundreds of different diseases. This is of great practical importance to both physicians and patients, because different cancers have to be treated differently having different outcomes for the patients. In this regard, recent studies have shown that we should classify and also treat tumors mainly based on the mutations that they carry other than the tissue of origin (see more in the article “Mutational landscape and significance across 12 major cancer types” by Kandoth et al. on Nature). Multiple genes are defective in cancers. Cancer does not occur from a single gene mutation in a single gene. Instead, the development of cancer involves multiple mutations within several key genes, including mutations in proto-oncogenes, tumor suppressor genes, DNA repair genes, etc. Researchers recently pointed out that we should start treating tumors based on their genetic and genomic profiles and landscape. These findings lay the groundwork for the development of personalized therapies. In addition, it is clear that pathways of genes should be the focus of treatment (see the comment “Herceptin pioneer’s life science innovation: Cancer pathways should be treatment focus” at MedCity News). These pathways of genes represent the driver defects that could be the cause of the disease, thus providing windows of opportunity in therapeutics (see more in the article “Comprehensive identification of mutational cancer driver genes across 12 tumor types” by Tamborero et al. on Nature). In the future, cancer will be a chronic disease controlled by an array of medicines each targeting a defective pathway of that specific tumor. Cancers will soon be classified based on their genetic profiles instead of the tissue of origin. Drug companies are already starting to adapt to this trend and new cocktails of more targeted therapies are on the horizon (Image Source: FOX News).

Every scientist is a kid in the purest way. Science has the potential to amaze, transform and inspire the way every single person on earth thinks of the world and themselves. The parallel between children and science is simple: every kid always wants to know the “whys” of things. When I was a kid, I remember being very curious about everything. I wanted to know every detail on the world surrounding my family and me. This characteristic even drove my mother crazy since she used to call me the boy of the “whys”; but it was the indication that I wanted to be a real scientist. This feeling got even deeper when in high school I had a biology teacher that gave classes on genetics and Mendel’s law. That was the moment I knew I wanted to work with genetics! And why am I writing about this curiosity that was always haunting me? Well, science is cool because we can try (at least…) to understand the “whys”. The instinct of curiosity is inside every kid, shy or outgoing, because children is always asking about the stuff around them. Kids in secondary school routinely carry out scientific experiments for classes and science fairs. However, the “discoveries” and/or “inventions” presented by them are never published; except for the kids from a group of British schoolchildren that might be the youngest “scientists” ever to have their work published in a peer-reviewed journal. The article was published in Biology Letters, and is authored by twenty-five 8- to 10-year-old children from Blackawton Primary School. These kids reported that buff-tailed bumblebees can learn to recognize nourishing flowers based on colors and patterns (see their article “Blackawton bees” here). The kids from this school asked the questions, hypothesized the answers, designed “games” to test it (which corresponded to the experiments), analyzed the data and wrote the article in “kids language”. Of course all of this had adult supervision by the British scientist Beau Lotto and teachers from the Blackawton Primary School (see more information in the article “Schoolchildren announce bumble-bee breakthrough in top science journal” from The Guardian). Using simple puzzles to direct bees to colors having sugar or salt, the kids discovered that bumblebees can use a combination of color and spatial relationships to decide which flowers they are directed to; this indicates that bees can indeed “memorize” information. In real life this might mean that bees are able to collect information and remember it when going to different fields in nature. The article was featured in a TED Talk by Lotto and one of the students named Amy O’Toole (all twenty-five kids were authors of the article) and also in a Featured Editor’s Choice from the prestigious Science Magazine. In addition, there was a special comment about their article in the journal that it was published and discussions about it in the scientific community all over the world. After this breakthrough (I mean the first kids publishing their discoveries in a peer-reviewed journal), it is a fact that the students of Blackawton Primary School are very lucky because they have had an educational experience which, sadly, most school science students never get to have (and I myself didn’t). They carried out a genuinely original piece of work and published it, or in other words, they went through all the scientific process from discovery to publication (it is worth to note that it took almost 2 years from the time of writing to the acceptance and publication of the article!). The kids also wrote in their article a conclusion that every scientist has come to at one point in their career: “Science is cool and fun because you get to do stuff that no one has ever done before”. Well, I wanted to describe this exceptional example about the kids from Blackawton Primary School to show that every scientist is like children – we want to know the answers to the “whys” in the world surrounding us. It does not mean it is an easy job, but that is why we love what we do!

The topic of this blog post is controversial and I would say “intriguing”. I just came back from Europe and watched some presentations of different researchers in a very “cozy” city called Bergamo in Italy. The most interesting talk was about the “hygiene hypothesis”. Well, humans have a very strong aversion to worms in general and one of these are helminths (the so-called “old friends” in the title of this post) that colonize our gastrointestinal tract. These worms can be pathogenic, cause digestion discomfort and they are uncommon in the developed countries but still occur in poor countries and the ones under development. In fact, there is an inverse correlation between the percentages of autoimmune disease incidences in the world and helminth infestation (see figure above). Recent research by several epidemiologists has shown a paradox with an opposite view of helminths suggesting that the recent increase in allergic and autoimmune diseases such as, for example, Multiple Sclerosis, occurred mainly because of increased improvement in sanitation (see the editorial “Helminths and multiple sclerosis: Will old friends give us new treatments for MS?” for more details). Even more disturbing is the suggestion that helminths may protect humans from autoimmune diseases and also allergic reactions. To prove this hypothesis, researchers did an experiment with Multiple Sclerosis (MS) patients. One group of patients was infected with helminths and the other wasn’t. After some time, the symptoms of MS patients infected with helminths disappeared and the ones without the worms worsened. These results are unexpected but have a scientific explanation: the improved control of the MS patients’ symptoms was associated with cellular immune responses characterized by decreases in immunomodulators and increase in other factors with concomitant induction of imunne regulatory cells (for more information see “Helminth-derived immunomodulators: can understanding the worm produce the pill?”). Essentially, in the infected MS patients it was if gastrointestinal helminth infection acted as a virtual immunological “switch”: when present helminths significantly turned off MS activity; however when helminths were removed by drug treatment, MS activity was turned on again. These results are controversial and more research is needed to understand why the worms can turn the MS activity off, but they are indeed intriguing. If the increase in autoimmune disorders and allergic reactions is associated to the elimination of worms in the developed countries, the “hygiene hypothesis” could explain more than we think about this increase in autoimmune diseases. Another fact worth to mention is the increased use of antibiotics in the developed world: in fact, microbiome research is showing that the microbes in people with autoimmune diseases such as Crohn’s and IBD is different from people without the disease. These new insights and theories that are emerging will be very important for a better understanding of why there has been an increase in autoimmune diseases in the developed world. The answer could be in the worm and microbe population that were always in “symbiosis” with our body and now we are “killing” them. New studies are warranted, but the worms are more important than we have thought for sure…

DNA does not make who we are, this is a fact now. Forget everything you know or think you know about genes. Recent years have accumulated scientific evidence suggesting a completely new paradigm based in the influence of the environment in changing our fate and destiny. The environment includes the diet, smoking, lifestyle, etc. Of course the genetic background is very important, but recent studies have been showing a different side of the history which is basically linked to an exciting field named epigenetics. This field studies the relationship between the environment and our genes at the organismal level. At the molecular level, it represents changes in our genetic material, especially the DNA, which modifies the structure of it without changing the blueprint of the sequence. Epigenetics has a major impact in changing gene expression and is affected directly and indirectly by the exposures we have before and after our birth. The findings in the field of epigenetics represent perhaps the most important discovery in the science of hereditary since the discovery of the gene. One classical example of the impact of the environment is the effect that the mother’s milk has for newborns (see the article “Mother’s milk: A rich opportunity” in Nature, 2010 by Anna Petherick). It is clear that breast milk feeding can affect brain development of the infants mainly as a consequence of changes in gene expression. These changes are mostly associated to compounds in the mother’s milk that affect the epigenetic mechanisms in the babies’ DNA. Lack of breast-feeding is also associated to increased risks of diseases such as diabetis and auto-immune disordes. In addition, a large study named ALSPAC (Avon Longitudinal Study of Parents and Children) has offered important insights on how the environmental pressures can influence health and development: baby lotions with peanut oil may be partly responsible for the rise in peanut allergies, high maternal anxiety during pregnancy is associated with later development of asthma by the kids and little kids who are too “clean” or living in a clean environment can have increased risks for eczema. Interestingly, epigenetics also pose a challenge for evolutionists since it brings back some of Lamarck’s theories and give us cards to play (if we are playing poker in the game of evolution…) against Darwin and his hypothesis. Lamarckism proposes that the environment directly affects the organisms and that the acquired changes can pass through generations. On the other hand, Darwin argued that evolution works indirectly through impartial selection – the more adapted would live and procreate. For a classical example, Lamarck believed that giraffes acquired long necks because recent ancestors had to get food in high trees that were rich in nutrients. For Darwin, long necks of giraffes evolved during millennia because genes for long neck had slowly gained advantage to these animals against their “competitors” with shorter necks. The conclusion is that our destinies are a product of a complex interplay between our genes and the environmental stimuli dynamics, such as the influence of our parents lifestyle, our lifestyle, diet and places we had lived. It will take geneticists several years to work out all these new implications, but we can be assured that the age of epigenetics has arrived to stay!