N.B. This science review was originally published in Optimyz Magazine in February 2012 by Mandy Wintink, PhD. 

My academic grandfather (i.e., my PhD supervisor’s supervisor), Dr. John Pinel from UBC, was the first person I heard argue that males and females are better considered along a continuum of maleness-femaleness rather than as a dichotomy. Considering sex along a continuum may, indeed, may be difficult, but there is substantial biological reason to suggest we are better off doing so if we are interested in more accurately understanding male-femalesness.

First, consider the genetics of sex. We categorize sex according to the chromosomes X and Y. Males have an X and a Y and females have two Xs as their 46th chromosome. Mothers pass on their X chromosomes to offspring, because they only have Xs, whereas fathers pass on both their X and Y. When the combine during fertilization, they give rise to either a male (XY) or female (XX). During normal development subsequent  sex-specific hormones - testosterone and estrogen - are produced and circulate through the body to give rise to what we typically think of as males and females, respectively.

At face value, this is simple to understand, until, of course, we consider that there are conditions under which there is a discrepancy among the genetic sex, the individuals response to sex hormones, and physical sex-specific characteristics like genitals and body type - medical conditions called “intersex”.

Here’s one example of intersex. A person has XX chromosomes and ovaries, but developed male external genitals. This results when a female fetus receives too much exposure to the masculinizing sex-hormone testosterone during critical periods in the womb. The labia (lips of the female external genitalia) fuse forming a scrotum and the clitoris enlarges to form a penis. Both of these tissue can develop in either direction, normally, and do so in response to circulating sex hormones (the default is female, btw). The most common cause of this is Congenital Adrenal Hyperplasia, a condition in which the individual lacks the a specific enzyme and effectively increases androgen (a hormone group that includes testosterone).

A similar condition, Aromatase Deficiency, happens at puberty. Aromatase is an enzyme that converts androgens to estrogens. This conditions goes unnoticed until XX girls hit puberty and respond to the excess of testosterone by beginning to develop into teenage boys!

Similarly, there are individuals who look like a woman but are genetically XY male. We tend to hear about these women around the time of olympics when questions concerning their exceptional performance evolve. In this condition, the individual is biologically unable to respond to androgens and therefore develop as females (the default remember). This condition, Androgen Insensitivity Syndrome, can go unnoticed by women until they attempt to have children and realize they have male, not female, internal organs.

These examples beg the question, what constitutes men and women? Is it genetics? Physical characteristics?  Gender identification? And I didn’t even get to touch on individuals who are XYY or XO genetically!

I find this topic really interesting to bring up for several reasons, particularly as a reminder that categories, although helpful in many circumstances, limit our understanding. I also hope, in highlighting this science, to promote tolerance for those who don’t fit into such categories, which can include varying sexual orientations. On that note, I will leave you with this final science tid-bit: There are several brain areas that specifically correspond to being male or female and develop later in prenatal development compared to genitals, suggesting a potential a mechanism by which gender and physical characteristics can be misaligned, like in transsexual individuals who undergo sex-reassignment surgery. There is significant evidence that these areas correspond to the sex felt, not born as (see research by scientist Dr. DF Swaab for many studies in this area). 

Blog Info:
In 2009 I reviewed how hormones work and discussed the effects of pseudo-estrogens (like Bisphenol A) on reproduction. I have reposted it on my A Science Perspective blog for those interested.

AuthorMandy Wintink

N.B. This science review was originally published in Optimyz Magazine in January 2012 by Mandy Wintink, PhD.

Epigenetics & Cancer

We have all likely been touched by cancer either directly or indirectly. The most prominent time for me was when my grandmother was diagnosed with colon cancer 13 years ago. It forced me to evaluate the role my diet could have on the development of cancer inside of me.

Although the exact causes of cancer are unknown, it is clear that cancer cells have an abnormal capacity to divide uncontrollably and form tumors. More recently, epigenetic changes are becoming important pieces of the cancer puzzle. Epigenetics are giving us insight into how cancer is triggered and progresses and how we can intervene in the development of cancer.

Epigenetics, as mentioned last issue, is the study of heritable changes that lie outside of the DNA sequence. Whereas genetics involves the code of the DNA, and for example, whether a gene is present or not or whether a gene has undergone a mutation, epigenetics primarily involve 1) the silencing and activation of genes through altered DNA methylation patterns, 2) histone modifications, and 3) chromatic remodeling - all of which alter gene expression.  Genetics are relatively stable, but epigenetics provide a mechanism for how the environment (including diet) can have an effect the expression of a person’s genes.

DNA methylation is the best known epigenetic marker. It’s the footprint the environment leaves on the DNA. It is also well known for its role in many forms of cancers. For example, hypermethylation in specific DNA regions silences genes that suppress tumor growth (known as tumor suppressor genes), which leads to tumors (and cancer). Alternatively, hypomethylation activates specific genes that are known for their potential to be cancerous. These genes are known as ‘oncogenes’ and their activation also leads to cancer.

Diet can affects DNA methylation and can affect some types of cancer, like colorectal cancer (CRC). There are recent estimates that diet can prevent up to 80% of CRC. The relationship between CRC and diet was first recognized when scientists noticed that CRC was much higher in Westernized societies, where people consumed high-calorie diets and were less physically active. It was then discovered that there are specific parts of a diet that both promotes and prevents cancer. For example, red and processed meat, substantial consumption of alcoholic drinks, body fat and abdominal fatness are believed causes of CRC, as is food containing animal fats or sugar. On the other hand, foods containing dietary fibre, garlic, milk, calcium, folate, vitamin D, and selenium,
as well as non-starchy vegetables, fruits, and fish seem to protect against CRC.

The dietary effects on cancer seem to happen two ways: directly, by affecting the gut lining, and indirectly, when the blood content of specific nutrients and hormones shift the body homeostasis in a negative way, resulting in genetic and epigenetic changes, including the silencing of tumor suppressor genes.

Altered DNA methylation in many cancers, not just CRC, show promise as a biomarker for cancer susceptibility. This is important because some of the methylation changes occur prenatally and in childhood long before cancer develops. By having a marker, lifestyle changes could be adopted to reduce future incidences of cancer manifesting. This concept coincides with Dr. Alfred Knudson’s 25-year old 2-hit theory of cancer, which is currently a popular way of understanding that it is not just one factor ultimately causes cancer.

Alterations in DNA methylation is also reversible, even through diet, and potentially under some of our control. This exciting area of epigenetics and diet have paved the way to a new field now called ‘nutrigenetics’. Needless to say, epigenetics serves as a promising areas of cancer research in everything from causes to biomarkers to therapeutic intervention. If this interests you further, I would suggest checking out http://www.dietandcancerreport.org/. 

AuthorMandy Wintink

N.B. This science review was originally published in Optimyz Magazine in September 2011 by Mandy Wintink, PhD.

Inheriting Our Parents Life Experiences

Still wondering about the nature-nurture debate? It seems rather clear by now that what we end up as is an interaction between our genes and the environment in which we exist. One of the ways in which this interaction happens is through a phenomenon called ‘epigenetics’. Whereas genetics has to do with the structure of the DNA sequence that codes for our genes and is passed on from generation to the next, epigenetics has to do with genetic changes and inheritance that lie outside the DNA sequence and involves biochemical changes that affect the expression of genes.

Epigenetics is a sort of imprinting, whereby the environment leaves its footprints on the DNA. This happens through a process called “DNA methylation” (an addition of a methyl group to the DNA sequence) or “histone deacetylation” (a transfer of the acetyl group to Co-enzyme A). The consequence of these two mechanisms is a suppression in gene activity, or the reverse effect if DNA demethylation and histone acetylation occurs. In the former case, the DNA stays tightly wound and is less able to express itself resulting in a suppression, whereas during the latter case, the DNA loosens and is more free to express itself resulting in heightened gene expression. What’s really interesting about epigenetics is that these changes can also be passed on to the next generation, providing a biological mechanism for a parent to pass on life experience.

How we respond to early life experiences is a great example of some current epigenetic research. Montreal researcher Michael Meaney has been using a rat maternal care model to investigate this. He has shown that when rat pups receive good maternal care (i.e., lots of licking, grooming, and nursing) they grow up to be less fearful, show fewer signs of physiological stress, and, if female, provide better care for their young.  He has also shown that these behaviours run in families.  Having a good mom means that rats are more likely to be a good moms themselves and that her offspring are less fearful, show fewer signs of stress, and also become good moms.

These behaviours continue across generations unless of course, you’re swapped at birth!  Meaney placed pups born to bad moms with good moms and vice versa.  Surprisingly, the pups took on the behaviours associated with the maternal care they received, not the behaviours associated with the maternal care of their biological moms.  What this meant was that the environment had a greater impact on how rats would turn out as adults than did the genetic lineage.

These results were so fascinating that they were published in the very prestigious journal, Science, in 1999. Then in 2004 Meaney’s group showed that these effects were happening epigenetically and were passed on to subsequent generations. They found changes in DNA methylation and histone deacetylation that were associated with both the rats’ early life experiences and the behaviours and physiology they developed in adulthood. And even though they changes were passed on, if they pups were swapped at birth, the effects were reversed, further confirming they were epigenetic and not just genetic.

Even more convincing of an epigenetic mode of inheritance, was when Meaney’s group chemically blocked the DNA methylation and histone deacetylation in the pups raised by bad moms. When they blocked these epigenetic changes the pups grew up to behave and show signs of stress as if they had been reared by good moms! This showed, without a doubt, that epigenetic changes were necessary for the early life experiences to dictate the future of the pups. And when those changes were blocked, the environment could not leave its footprints. 

AuthorMandy Wintink

N.B. This science review was originally published in Optimyz Magazine in June 2011 by Mandy Wintink, PhD.

In my sports bag, I have my frisbee gear, cleats, band-aids, hair elastics, and cliff bars. About 3 years ago I swapped my Ibuprophen for Arnica Montana, upon consultation with our team Naturopathic Doctor. 

Arnica Montana is a homeopathic remedy for injury and inflammation. Homeopathic remedies are often scrutinized, largely because the medical philosophy under which they are prescribed are counter-intuitive to the way many of us think.

Homeopathic remedies function on the like-cures-like philosophy. The best analogy with Western medicine is to vaccinations, where small amounts of a known causal agent (like last year’s flu bug) are given to a person to help stimulate his or her own immune system and to develop antibodies, with the hopes that those antibodies will launch an attack should that foreign invader enter the body in the future. Homeopathics, on the other hand, are given to stimulate a person’s own healing processes at the time of the illness or injury. Another main feature of homeopathic remedies is that the amounts given are exceptionally small. In fact, according to its philosophy, lesser, not greater, amounts produce a more potent therapeutic!

These very small amounts are, in fact, so small that the actual substance itself is not even present, just the molecular or energetic resonance of it once being there. Homeopathics are prepared by diluting the original substance over and over and over again. The more diluted, the greater the strength, and the higher the number on the homeopathic container (e.g., 6C, 30C, 200C).

General skepticism exists among medical doctors and scientists believing that there cannot possibly be any biological effects in such diluted substances. However, Nobel Prize Laureate Luc Montagnier, the scientist who discovered HIV, disagrees. Dr. Montagnier is currently researching the structural changes in water produced by the DNA of bacteria after really high dilutions. Although he does not study homeopathy himself, in an interview with Science magazine in December 2010, he was specifically asked what he thought about homeopathy, because of the parallel to his research. He responded by stating that what he knows is that high dilutions are not just nothing. They leave residues in the form of electromagnetic resonance. He did qualify his answer by saying that his own research was not using as high of dilutions as homeopathy does but that even at 10-18, when he cannot detect a single DNA molecule of the bacteria he can still detect the electromagnetic signals.

This line of research is actually quite exciting for homeopathy. Until recently, the science on homeopathy hasn’t been so hot. With hundreds of homeopathic remedies out there, some researchers have attempted to answer the simple scientific question “does homeopathy work?”  Many studies, and studies of studies (i.e., meta-analyses) suggest it does not. There are a limited number of both good- and bad-quality studies demonstrating therapeutic effects of several homeopathics, but an even greater number have yet to undergo the scientific scrutiny. All of this just goes to show that us scientists don’t know the answers yet!

So why do I still carry arnica in my bag? I did read a few convincing studies. For example, a 2007 study did show that topical arnica was as effective as corticosteroids for reducing edema following surgery. Given that corticosteroids are known to have negative side effects, an alternative would be welcomed. Also, a research group in Brazil has focused on Arnica 6C and shown many positive results, for example, in an animal and cell-culture model of inflammation, arnica reduces a variety of inflammatory chemicals in the body. In a study published this year, they also reported that the therapeutics effects were only visible in those who had a delayed inflammatory response, rather than an immediate response, which begs the research question, why is this? The authors suggest individual differences are important factors to consider. And so would homeopathic doctors!

Homeopathy is actually much more complicated than our current way of doing medical research can handle. We also must remember that science is a tool, not the final answer, and together with other pieces of evidence, science helps form the big picture.

AuthorMandy Wintink