Category Archives: Science

Medical, Research, Science

How Do Our Genes Make Us Human?

MOLECULAR BIOLOGY

Intro: One thing common to all life on Earth, from bacteria to blue whales to bonobos, is a genetic code contained within strands of DNA. This leads to the perplexing question of how our DNA creates human beings.

LONG sections of genetic code are identical across the entire span of life. About 50 per cent of our own DNA sequence is the same as bananas’, while we share 98 per cent of our DNA with chimpanzees. So, what makes us different?

In April 2003, a major milestone in the study of human genetics was reached with the publication of the complete human genome. An enormous collaborative project worked on by scientists in 20 different countries, it may well come to be regarded in the same light as the great scientific landmarks. Principal among these was the work of the Augustinian monk Gregor Mendel – often referred to as the “father of genetics” – which he carried out in the 1850s and ‘60s and which first established the rules of heredity, as well as James Watson and Francis Crick’s 1953 description of the molecular structure of DNA as the now-famous double helix.

Gene Expression

The published genome contains the sequence of some three billion so-called base pairs, which constitute the genetic code in our DNA. The translation of the code made up by these base pairs is used to build up 20 different essential amino acids which, together with other amino acids we get from our food, combine in numerous different ways to form all the different proteins we require in our bodies. Geneticists used to think that the role of DNA was almost entirely concerned with providing a template for the manufacture of these proteins, but the complete genome showed that the sections of DNA which perform this function, our genes, only account for about two per cent of the total.

The function of the remaining 98 per cent, sometimes known as “junk DNA”, is not entirely known, but it has become increasingly apparent that much of it is not junk at all. It plays a role in, among other things, gene expression. This is the actual process by which the information contained in our genes is used to make up all the different tissues and organs in our body, through the process known as cell differentiation. Here, stem cells divide to produce different types of cells, such as liver cells or nerve cells. Unravelling the way in which one type of cell divides to produce a wide variety of different cells has proved to be extremely difficult and is currently one of the principal areas of genetic research.

The basic functioning of DNA in producing amino acids from the genetic code is relatively straightforward: the double-stranded DNA molecule effectively unzips, splitting apart the base pairs and revealing the code that is then copied by single-stranded RNA and used to assemble amino acids. But the control of this process, in which the required genes are activated and those not needed switched off, appears to be extremely complicated. Each advance in our knowledge of gene expression uncovers a whole new level of complexity that has to be unravelled. Beyond that, there is also the equally tricky problem of determining how, during the process of protein folding, the proteins made from genes assume the three-dimensional shape that determines their functions. The potential applications of our advancing knowledge of gene expression and protein folding are wide, not least in increasing our understanding and ability to treat diseases which have a genetic basis, prominent among which are many forms of cancer.

The Difficulties of Cloning

Another landmark in genetic research was achieved in 1996, when the first mammal (known as Dolly the Sheep) was cloned by geneticists at the University of Edinburgh in Scotland, using a technique called somatic cell nuclear transfer. This involves the removal of a nucleus containing genetic material from a cell of the animal to be cloned, and its introduction into an egg from which the original nucleus has been removed. The egg is then implanted into a surrogate mother and, in theory at least, will develop into an embryo with DNA identical to the animal from which the nucleus was taken.

Needless to say, if it were as easy as that, cloning would be a common occurrence today. In reality, it has proved much more difficult, in part because of the complications which arise as a consequence of gene expression. In some successful cloning experiments, for instance, the observable traits, or phenotype as it is known, of the cloned offspring are not always the same as those of the original animal. So, despite being genetically identical, the offspring looks different from the parent. In order to produce exact copies of the original, the process of cloning has to solve the complicated issues involved with gene expression, including the role of junk DNA in regulating genes. We are, it appears, a long way from seeking flocks of cloned sheep.

Alternative Theories

In recent years, it has become increasingly apparent that gene expression is not controlled solely by DNA but is also influenced by a number of external factors collectively known as epigenetics. This is a new field of scientific research and the details of how it works are disputed, but, in essence, it implies that the environment in which DNA replication occurs during cell division can influence the activity of genes and, in doing so, can have an effect on the resulting phenotype. This is thought to occur at a molecular level, through environmental factors modifying the actions of those proteins that surround strands of DNA and influencing the switching off or activation of genes. These epigenetic modifications do not change the DNA sequence of base pairs, so are not inherited by future generations, even if those generations may then be subjected to the same environmental conditions as the parent, resulting in similar epigenetic modifications.

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Health, Medical, Research, Science

Injection of antibodies could reduce risk of heart attacks and strokes

MEDICAL RESEARCH

THOUSANDS of lives could be saved every year after scientists discovered a group of antibodies that dramatically reduce the risk of heart attacks and strokes – and revealed plans to develop an injection of the substance for those most at risk.

The researchers say their discovery could lead to the development of a test to determine a person’s risk of heart disease within three years and an antibody injection to protect them in as little as five years.

A lead researcher at Imperial College London, said: “If this line of research is successful it would mean a revolution in tackling the biggest killer in the world.”

Everybody has at least some of these antibodies, but levels vary widely between people and that plays a crucial role in determining how likely they are to suffer life-threatening heart problems.

The effect of the antibodies is so profound that people with high levels of them are 70 per cent less likely to develop heart disease than people with low levels of them.

High levels of the antibodies show their hosts have less of the dangerous plaques in their arteries that cause most heart attacks and strokes.

The discovery has the potential to save numerous lives, leading heart specialists have said.

More than 100,000 people in the UK die each year from a cardiac arrest or stroke that has been caused by plaque on the inside of an artery. By discovering which patients have plaques that are more likely to rupture and why, thousands of lives a year could be saved.

The development of new drugs might be used to tweak the immune system to prevent people from having a heart attack or stroke.

The British Heart Foundation is known to have funded much of the research and has given Dr Khamis – a consultant cardiologist at Hammersmith Hospital – £1million to develop his work further. He is working on a blood test to identify people at high risk of heart disease by measuring levels of the antibody. He hopes this will be available on the NHS in the next three to four years.

Those people identified as being most at risk can then make lifestyle changes to reduce the threat.

Even more significant, Dr Khamis is also developing an antibody injection that could be given to patients at high risk, which he hopes would be available in the next five to ten years.

However, he cautions more research is needed on both the test and the treatment to confirm their effectiveness before they could become available.

Scientists do not yet fully know why some people have higher levels of the antibodies.

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Biotechnology, Government, Health, Medical, Science, Society

Genomic medicine is being blocked by the NHS

NHS: GENOMIC MEDICINE

THIS MONTH the NHS will become the first health service in the world to offer whole genome sequencing to patients where clinically appropriate. Heralded by NHS leaders as “a new era of genomic health”, the goal is to use these data and new technologies to decode and treat previously intractable diseases, to move away from symptomatic treatments to cures and prevention.

The Prime Minister has said she wants the UK to lead the world in this new area of science – to continue a tradition of innovation in this country that will “extend horizons and transform lives”.

Theresa May’s ambition to lead the world in genomics and precision medicines is one that we should all want to support. Scientists and doctors know that pioneering precision medicines and their advances change lives, but they will also be aware of the challenges that must be overcome to realise its potential. This is not necessarily because the science is lacking, but because a fundamental shift in thinking is still needed by governments, regulators and policymakers in how they assess the value of this innovation.

Cystic fibrosis (CF) is an excellent example of this challenge. In 1989, when the cystic fibrosis gene was first identified, scientists did not know how mutations in the gene caused the condition. There was nothing to treat the underlying cause of the disease and people could only seek treatment for their symptoms.

After nearly 20 years of research and development by hundreds of scientists, and the design, synthesis and testing of more than 400,000 unique molecules, they have now done what was once thought impossible – discovered and brought to nearly half of all CF patients the first medicines to treat the underlying cause of this devastating disease. Today, multiple medicines approved by the EU and U.S. now exist, and there are more coming down the line. The ultimate goal is to cure CF once and for all.

For this remarkable cycle of innovation to be completed, Governments must now play their part, by providing patients with access to these medicines. Three years after approval of these medicines, this has still not happened because scientific innovation is outpacing the UK medicines evaluation system.

The evaluation criteria and processes used by the NHS and the National Institute for Health and Care Excellence (NICE) are currently preventing them from being made available to patients. Despite universal acceptance of the benefits that these medicines will bring, people in the UK have been waiting for access for more than 1,000 days, while thousands of people with CF in other countries in Europe and the US have been benefiting from them for years.

CF patients don’t really have the time to wait. Half of those with this cruel disease will die before they are 31. Science has delivered the breakthroughs, but the system is blocking access. The UK has the second largest number of CF patients in the world.

In 2016, the UK’s own chief medical officer recommended a fundamental shift in how new transformative medicines are developed and appraised for use in healthcare systems. The appraisal system in the UK needs to reflect that the genes and pathways underlying genetic diseases seldom respond to traditional pharmaceutical approaches, and so precision medicine requires risk-taking innovation.

The Life Sciences Industrial Strategy, a report made to the Government just last year, echoes many of these sentiments. It outlines the need for industry to take on bold, far-sighted ambitions in the life sciences with the intention of creating commercial success, underpinned by novel technology and higher-risk science. The strategy singles out a handful of successful biotech companies with highly innovative products. Yet, unlike in many other European countries, the NHS and NICE have not yet followed these recommendations and evolved their evaluation criteria for these types of transformative precision medicines.

The Government must surely need to act, not just for more than 10,000 people currently living with CF in the UK, but also for people suffering from many other kinds of genetic diseases.

Genomic medicine stands on the cusp of becoming an everyday reality. Those institutions at the cutting edge of gene therapy and gene editing need a system that is already thinking about the innovations of tomorrow. Such systems need to incentivise innovators to get medicines into the hands of patients as soon as possible.

Organisations involved in scientific advances will never give up on their ambition to cure serious diseases that today might still seem impossible to tackle. While they continue to deliver on the science, the UK Government must show its commitment to biomedical innovation if the genomic revolution is to be fully realised.

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