Medical, Research, Science

Will we ever develop a vaccine for HIV?

MEDICAL SCIENCE

Intro: In 1983, HIV (human immunodeficiency virus) was found to be the cause of a range of conditions collectively known as AIDS (acquired immune deficiency syndrome). Over 35 million people have since died due to HIV, and the same number live with it.

THE high number of HIV cases and deaths worldwide is in part because the antiretroviral drugs that have been available since the mid-1990s, allowing infections to be managed, are not always widely available in certain parts of the world – namely in Africa, where HIV infection rates are the highest. But also, unlike many other viral diseases, attempts to develop a vaccine for HIV have so far been unsuccessful.

Vaccination against a variety of infectious diseases is now such a routine part of healthcare that it is easy to forget how important it has been in the history of medical science. Many millions of deaths have been prevented since the principles of vaccination were established by the English physician Edward Jenner in the late eighteenth century. Jenner had become aware of local knowledge near his home in Gloucestershire; milkmaids who had previously caught cowpox, a relatively mild disease, did not then suffer from the similar but much more serious, and potentially fatal, smallpox. Jenner conducted trials in which he exposed people to cowpox and some weeks later to smallpox, finding that the more serious and virulent form of the disease did not develop as predicted. It represented the beginning of a long process, which culminated in 1979 when, after a decades-long programme of vaccination, the World Health Organisation (WHO) was able to announce that smallpox had been completely eradicated.

The Success of Vaccines

Great advances in our understanding of how vaccines work was made in the late nineteenth and early twentieth centuries by, among many others, Louis Pasteur, Robert Koch and Paul Ehrlich (the German physician and not the American environmentalist of the same name associated with the study of global population growth). The way in which the immune system works – through the production of antibodies – was discovered, and methods of producing vaccines extended from Jenner’s use of a related mild disease to the use of killed or weakened forms of the original infectious agent, allowing vaccines for a greater range of diseases to be developed. Vaccines were developed for one infectious disease after another, perhaps most famously including the vaccine for polio, developed in 1955 by the American virologist Jonas Salk.

The Trouble With HIV

In among the remarkable successes, vaccines for a few infectious diseases remain frustratingly out of reach. HIV has the ability to evolve quickly, making it difficult to produce a vaccine that will be – and will remain – effective against all the different strains. A further complication arises because it initially evolved to attack the immune system, which has given the virus a complicated surface structure that enables it to evade detection. Vaccines work by stimulating what is known as the adaptive immune system, the part of the system that can remember the structure of pathogens, so that when these are encountered again the immune response will be enhanced. In the case of HIV, the usual ways of producing a vaccine do not work because it is not detected in the first place, so the immune system is not stimulated.

As if the problem of producing a vaccine was not already complicated enough, further difficulties arise because the two usual methods for producing active agents for vaccines have not worked for HIV. Most vaccines have been developed using either a killed or deactivated (attenuated) version of the pathogen, so that it stimulates the immune system without causing harm. HIV that has been killed does not stimulate an immune response, while the complex structure of the virus means that attempting to deactivate it is difficult. Using an attenuated version would run the risk of infecting the patient.

A formidable range of obstacles still exists, but over 30 years of research have provided medical researchers with a huge body of knowledge on HIV, leading many scientists to be optimistic about a future cure. In the meantime, advances in the management of the disease mean that those with HIV, with access to the relevant drugs, can expect to lead an almost normal life. Until a vaccine is found, the challenge remains to extend these treatments to as many people as possible.

Alternative Theories

HIV suppresses the immune system by invading and attacking T cells, which play a crucial role in what is known as cell-mediated immunity. It was thought that, once the virus had invaded a T cell, it replicated and then spread to other T cells through the blood. Recent research has found that it can actually spread much more quickly, by utilising short-lived connections between T cells in order to transfer directly from one cell to another. This may help to explain why those vaccines developed so far have not been very effective, because these have only worked against HIV in the blood, and it may also open up the possibility of new forms of treatment that in some way block this cell-to-cell transmission.

Recommended/Supplementary Reading:

. National Geographic: Ancient “Giant Virus” Revived From Siberian Permafrost

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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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Arts, Education, Philosophy, Research, Society

Oxford academic to launch ‘journal of controversial ideas’

ACADEMIA & RESEARCH

A “controversial ideas” journal where researchers can publish articles anonymously will be launched this year by an Oxford University academic.

The journal is in apparent response to a rise in researchers being criticised and silenced by those who disagree with them. The revelation came towards the end of last year by Jeff McMahan, a professor of moral philosophy at Oxford.

“There is an increasing tendency that I see within academia and outside for people to try to suppress views they don’t like and treat them as wicked and unspeakable, rather than confront those views and refute them,” he said.

The phenomenon of attempting to shut down views you disagree with has become “very pronounced” among young people and those on the Left, he said, adding that academics also feared being censured by their university administrations.

He cited the example of Prof Nigel Biggar, a fellow Oxford academic, being “targeted” after he suggested that people should have “pride” about aspects of their imperialist past. More than 50 professors, lecturers and researchers signed an open letter expressing their “firm rejection” of his views. Prof Biggar later revealed that young academics were afraid of damaging their careers if they were seen with him.

Another example he gave was when the Oxford Students For Life group invited speakers to discuss the legislation surrounding abortion in Ireland. “They were shut down by a feminist group and unable to proceed,” Prof McMahan said.

A newly formed group of over 100 academics from UK universities has raised concerns about “the suppression of proper academic analysis and discussion of the social phenomenon of transgenderism”.

They said that members of their group had experienced campus protests, calls for dismissal in the press, harassment, foiled plots to bring about dismissal, no-platforming, and attempts to censure academic research and publications.

Francesca Minerva, a bioethicist at the University of Ghent in Belgium, approached Prof McMahan about setting up The Journal of Controversial Ideas after she received death threats due to her academic research.

She had to seek police protection following the publication of an article she co-authored in the Journal of Medical Ethics which defended the permissibility of early infanticide in a certain range of cases. Prof McMahan said that the new cross-disciplinary publication, which is due to launch this year, would be fully peer-reviewed in line with normal academic standards.

He said that he and Peter Singer, the prominent Australian philosopher, were assembling an editorial board that is made up of academics and distinguished people in their fields from across the political and religious spectrum.

OPINION

The publication of a new journal in which academics may write under pseudonyms, for fear of retribution, is truly alarming. The motive for the founding of this new Journal of Controversial Ideas is to avoid persecution by the universities that employ contributors.

This is not like a medieval inquisition; it is actually worse. In the High Middle Ages scholars publicly debated points of controversy – quodlibets, they were called – and no thesis was too outlandish to defend. Today we see closed-shop “academies”, in history or science, monstering anyone who dares to venture outside the fashionable consensus.

To suggest, for instance, that the British Empire had its good points and – bang – the solid weight of academe will likely fall on those making the claims. When even universities won’t favour free and open discussion, the resort to pseudonyms and anonymity convicts them of betrayal.

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