“Shall I compare tea ...?” A small change sometimes has a big impact. What applies to the quote from a poet can also be applied to life’s blueprint, the DNA. Small changes in our DNA can have far-reaching impacts on our body.
Following the decoding of the human genome in 2001 and the subsequent strides made in genome research, today we have a growing understanding of the impacts of our own unique genetic make-up and how it can be used. Besides individualised medicine and stratified drug therapy, these findings may also be used in future for personalised nutrition.
Ever since its discovery, the DNA molecule has fascinated us and divided opinion in equal measure. This is certainly also due to the predictive character of the molecule.
Each human cell contains an individual’s entire genetic information, which is stored in the chromosomes. Each chromosome consists of a huge ring-shaped molecule, the deoxyribonucleic acid or DNA.
Humans have two pairs of 23 chromosomes in each cell, corresponding to about two metres of DNA. DNA, in turn, consists of a strand of nucleotides. Each nucleotide contains one of the four bases adenine, cytosine, guanine and thymine (abbreviated to A, C, G and T), which form the genetic code. The genome formed by these letters (bases), which consists of 3.2 billion nucleotides in humans, contains the blueprint for the development of a human being from a fertilised ovum.
High variability of genotype and phenotype
But even when the human genome project began, we knew there is not “one human genome”, but that our genome, just like that of all other organisms, is extremely variable.
The human genome has more than three million defined variable sites. These variations often concern a single DNA building block. Besides such variations in individual bases, some individual bases can also disappear (deletion) or be added (insertion).
An organism’s individual set of genes is called the genotype. Genes, in turn, provide the blueprints for making proteins. The base sequence encodes the sequence of amino acids in a protein molecule, i.e. determines its composition.
Proteins play very important roles within a cell. They act as building materials (structural proteins), regulate metabolism and cell function in the form of enzymes, and transmit signals. The genotype therefore has great influence on an organism’s development and on the phenotype (the composite of an organism‘s observable characteristics).
Predictive genetic diagnostics
The direct relationship between genotype and protein structure is a simple one, but has serious consequences: changes in base sequence may lead to defects in protein formation. We now know that specific bases in the genome may vary greatly, i.e. are often different from one person to another. These findings are the basis for predictive genetic diagnostics, the early detection of diseases. This field of genome research remains highly controversial. After all, in purely technological terms, examination of the genome also makes it possible to diagnose a (possibly incurable) disease before symptoms manifest themselves.
Given the speed of technological development, the German legislature therefore perceived an urgent need to regulate the market for genetic analyses in Germany. The Genetic Diagnostics Act (GenDG, “Human Genetic Examination Act”) that entered into force in 2009 was the result of an arduous parliamentary process that was designed to weigh up the benefit of the findings obtained from these new technologies against the potential damage they may cause to the individual. In spirit, this act is based on the “right not to know” as the overarching goal. While this approach makes sense in principle, without a carefully considered and balanced discussion it may place genomic research and genetic diagnostics under the general suspicion of intending to damage the individual. This is neither true in substance, nor would such a view be conducive to societal debate on the individual usefulness of genetic testing.
Apart from predictive genetic diagnostics, which main purpose is to detect genetically based diseases at early stage, genome research has also done a great deal over the past 15 years to enhance our understanding of a patient’s highly individual response to drug therapies. There is now a very good scientific basis for the fact that many genomic variations also influence the effectiveness and tolerance of medicines. Owing to their individual genetic make-up, each person inevitably metabolises drugs in a slightly different way. Knowledge of these relationships forms the basis of so-called pharmocogenetics, which pursues the aim of providing the patient with an individualised and thus stratified drug therapy.
In contrast to predictive genetic diagnostics, which usually delivers probable findings, pharmacogenetic diagnostics generally provides very definitive findings. This has improved the basic acceptance of genetic analyses in recent years.
Wish for customisation
Nutrigenetics is another field that is developing very rapidly. In general terms, this looks into the relationships between nutrition and genetics, and it too is benefiting from the changing attitude towards genetic diagnostics. In this context, genetic diagnostics appears to have lost some of its horror, also in the public perception.
I see two main reasons for this, or related trends. Fundamentally, humans are very curious creatures. This curiosity had evolutionary benefits: our ancestors explored many things through trial and error that are useful to us today. Alongside our innate curiosity, we are now observing a further trend – the recognition of our own individuality and the resulting wish to go our own way. Industry has recognised this trend and is responding to it. The responses range from smartphone screens to customised muesli mixes and personalised shopping recommendations on online shops. Companies are proposing individualised or customized offers.
The spirit of our times obviously plays into the hands of the market for genetic analyses. “You are unique, and that’s how you want to be treated.” This trend is being fanned by the findings of genome research.
It therefore comes as no surprise that genetic diagnostics has moved on from exclusively medical applications and is increasingly involved in the so-called lifestyle segment.
Innovation and reflection
A contributing factor is that the technology used for such analyses has become ever simpler, faster and cheaper. It took almost 10 years to decode the first human genome, and cost billions of US dollars. As far back as 2009, the first start-ups astounded the still emerging market by offering to sequence a human genome for less than USD 100,000 within one month. Today, a genome analysis can be performed in just a few days for about USD 1,000. Nor is this technology likely to stand still. In future, everyone will be able to afford and have access to his own genomic profile.
But what is the use of all these data without correlations? The bare fact that analysis, i.e. data collection, is becoming ever cheaper and faster is not a direct indicator that these data provide an equally dynamic benefit. The age of data collection must be followed by a phase of reflective interpretation. The development of algorithms that translate genetic data into deterministic statements takes some time.
Nevertheless, some research institutions and companies, also in Germany and the rest of Europe, have set themselves precisely this goal. Next to predictive genetic diagnostics and pharmacogenetics, this has given rise to another branch in the past five years, so-called nutrigenetics.
The long-term goal of nutrigenetics is to be able to prevent specific diseases by adopting a diet that is adjusted to the individual’s metabolism.
Nutrigenetics examines the relationships between nutrition and genetics. In particular, it examines the extent to which genetic variations influence metabolic processes in the body and (nutrition-related) diseases. The long-term goal is to be able to prevent specific diseases by adopting a diet that is adjusted to the individual’s metabolism. For this, functional gene variants need to be identified that can be influenced by nutrition or nutrients. This is intended to lower the risk of disease in a targeted manner as a function of genotype.
A well-known and very old example in this context is lactose intolerance.
Not everyone can consume dairy products ad libitum. In some people, too much milk causes digestive symptoms and gastrointestinal problems. To digest lactose (milk sugar), the body needs the enzyme lactase, which these people do not produce in sufficient quantities. Lactase breaks lactose down into its constituents galactose and glucose. If lactose is not broken down, it cannot be absorbed by the body, but remains in the intestine and draws in water through osmosis. Finally, the lactose is fermented by intestinal bacteria, giving rise to gas (CO2). This leads to diarrhoea, bloating and belly pain.
In its original form, lactase is only formed to a full extent in the first months of a human life to enable the digestion of breast milk. It is then produced in lesser quantities because little lactose is taken in via food. The majority of the world’s population still displays this original form. In Asia and Africa, though, dairy products are not usually part of the people’s diet. In Central Europe, two genetic mutations became established that prevent a reduction in lactase production. People with both mutations produce enough lactase all their lives and can digest almost unlimited quantities of lactose. This form of the enzyme represented a real evolutionary advantage in those parts of the world where dairy farming was important. Today, only one in five to ten Central Europeans still bears the lactase gene in its non-mutated original form.
So, the resulting lactose intolerance is not an illness in itself. In fact, it is lactose-tolerant individuals who are the real mutants. However, only few people who suffer from lactose intolerance know that their bodies do not product enough lactase, and therefore consume dairy products without paying attention to their individual tolerance limit. That often leads to the side-effects described above. People who have undergone nutrigenetic examination and know of their congenital intolerance can reduce their daily lactose consumption and prevent possible digestive problems, impairment of their immune system and more severe resulting ailments. There is no need to completely dispense with dairy products, because almost all of them are now available in a lactose-free version. Nor would it be advisable to do so given the many nutrients that milk contains. If these are not available in our bodies, this often leads to malnutrition and resulting conditions such as osteoporosis. As this example shows, personalised nutrition is indeed more convenient than general dietary recommendations for initiating prevention strategies at an early stage.
Nutrition and common diseases
The relationships between nutrition and the emergence of more complex common diseases such as diabetes, obesity or high blood pressure are not so easy to correlate. However, these are precisely the areas where it is hoped that nutrigenetics will provide findings that can be used to prevent these conditions. The Food4Me (www.food4me.org/de/) initiative founded in 2011 collected data from voluntary test persons, which were meant to facilitate such correlations. The findings are intended to help develop new scientific tools that use nutrition-specific, genetic and phenotypic data to define a personalised diet.
A further aim is to examine whether it is easier to motivate people who are aware of their individual risk to change their behaviour, as compared with generally worded dietary advice. At present, no conclusive answer can be given as regards the extent to which genes influence nutrition-related diseases. Despite many correlations between gene variants and blood sugar, cholesterol or vitamin levels, the causes of diseases always involve a multitude of factors. The actual contribution genes make to the overall risk of disease, as compared with other risk factors, remains a matter of heated debate. No one can safely say at the moment whether someone who bears a genetic risk of developing diabetes will not do so in the long run due to a special diet.
However, practical success has already been achieved in nutrigenetic research. One example are people with a variation in the methylenetetrahydrofolate reductase gene (MTHFR gene), who have been shown to benefit from personalised dietary recommendations. People with a defined mutation in the MTHFR gene are less able to convert folate in its biologically active form. At the same time, their ability to convert harmful homocysteine into methionine is limited. The people affected therefore have a higher risk of an elevated homocysteine level, and thus of thrombosis and cardiovascular disease.
About 10% of the population carry this gene variation. It was possible to show that the affected people derived major benefit from a higher intake of folate or folic acid by eating folate-rich vegetables such as broccoli and spinach, or dietary supplements. This change in diet is obviously sufficient to normalise risks.
Beyond this, the findings of nutrigenetics may possibly be used in general for sustained and healthy weight loss. Some firms, also in Germany, are already offering genome profiling to make specific recommendations for a better lifestyle, optimum nutrition and dietary supplements. This is a very successful business model, given that almost one in two people in Germany would like to lose weight, according to a recent study by the Institut für Demoskopie Allensbach (Allensbach Institute). While the validity of these tests and the conclusions drawn from genome profiling are still being hotly debated in professional circles, sales are rising all the same. This can also be seen as a reflection of the prevailing spirit (Zeitgeist).
Although research into gene-based dietary recommendations is still in its infancy, this concept of individualisation will assert itself. After all, each of us is unique – and this is a good thing.