Yeast produces not only bread and wine

[The Leaven – exploring the relationship between science and religion (cont)]

The last post established why yeast is used as a model organism to study molecular biology but how and what is it used for? The last century saw a molecular enlightenment, yeast was cemented as a key component of that movement. In the 1950’s, molecular biologists constructed a  Saccharomyces cerevisiae strain containing biochemical markers (antibiotic  resistance or amino acid selection) known as S288C from the fig strain mentioned in the previous post, EM93. It was soon discovered that self-replicating elements of DNA found in bacteria called plasmids could also be made to function in yeast. Yeast cells multiply rapidly and the overall effect of a mutation in a certain gene can be measured biochemically or by observation under the microscope. If DNA fused to reporter genes is inserted into the self replicating DNA from bacteria and then introduced into the yeast cell, it can be propagated and then extracted. This technique is called cloning as it replicates an identical copy of a gene, has been used to mass-produce proteins and vaccines. In yeast, cloning was used as early as 1980 to produce Hepatitis B vaccine. Since then it has produced a multitude of proteins and vaccines including: insulin, growth hormone, haemoglobin, oestrogen receptor and interferons.

Cloning can also take place in bacteria such as Escherichia coli, these cells divide faster than mammalian cells but are a lot smaller so there is a limit in the size of the protein that can be cloned. As a consequence of this other cells types are now also used for cloning such as those derived from mammals, insects and viruses. Cloning provides an extremely economical way to reproduce human proteins. They replace the need for animal production and reduce the risk of transferring unwanted diseases, such as, CJD from growth factor. Although great advances have been made, the systems are still not perfect and have their limitations according to the type of protein that can be cloned, as some are toxic to the cell, and introduction of unwanted mutations occurs far more frequently when selection is not acting on the protein. Most organisms, including bacteria, have their own DNA repair systems that detect mutations. Foreign DNA has a higher chance of retaining mutations in a host cell as it is not detected through normal cell function, a problem to biotechnology that is successfully addressed in natural systems by selection. The use of these systems with limitations causes uncertainty and increases risk factors, subjects which are discussed  in future posts. It seems yeast occasionally retains its Biblical ability to behave in a corrupt way.

Protein interactions: Ribonuclease-inhibitor protein grabbing and surrounding the ribonuclease A enzyme. Image by Dcrjsr.

Following the heady days of protein engineering, yeast laboratories, through intra-science communication, successfully completed the enormous challenge to complete the first fully sequenced eukaryotic genome. This was achieved using strain S288C and relatively archaic apparatus compared to the robotic systems used to decode the human genome. Eventually, over 6,000 genes were unravelled from the yeast nucleus. The yeast genome is 200 times smaller than the human genome but almost four times larger than that of E. coli. This achievement marked a milestone in biological history. Yeast biologists did not stop at just sequencing the genome. In a striking example of inter-organisation collaboration, nominated laboratories began deleting single genes from individual yeast cells through advances in polymerase chain reaction (PCR), a technique that can amplify a single gene from the cells DNA. A marker/reporter gene flanked by target DNA is amplified by PCR technique and then inserted into the yeast cell. Non-homologous recombination replaces the genomic gene with the introduced marker/reporter gene. Biochemical tests were then carried out on the mutant yeast strains to uncover the functional analysis of hundreds of different gene products. This work elucidated many gene functions and undoubtedly contributed to the discovery of many analogous human genes. This information has been collated into several databases to provide a plethora of data available for bioinformatics across the internet. Genes placed on microarray slides and subjected to various environmental conditions and variations of DNA recombination techniques have increased the quantity of this information, enabling researchers to compose complicated hypotheses and uncover new cell processes without even entering a laboratory.

Many would expect yeast’s contribution to scientific research to stop at this point. Exhausted by constant, investigative probing. In contrast, the yeast story continues. It has also been used as a vehicle to investigate protein interactions first with native yeast proteins and then later with proteins from any other organism. Genes can be fused to protein tags, introduced into yeast cells and reporter genes within the cell can detect if the proteins produced from the introduced DNA interact. This procedure is known as the yeast 2-hybrid technique. Several variations to this technique exist, again modifying it to be used in other in cell cultures from other organisms. These techniques, in a rudimentary way, can also be used to evaluate post-translational modifications in proteins, to see how gene products are modified by the cell. Compared to the amount of gene sequencing data available the amount of protein interaction data is still fairly incomplete with the function of many gene products still unknown.

…only humans can create green mammals

[The Leaven –  exploring the relationship between science and religion (cont)]

Through their pursuit of knowledge and solutions, scientists sometimes have adopted unorthodox methods that have clashed with the moral objectives of religious organisations. The aim of recorded information in the Bible is to influence and manipulate human behaviour and to this end it is very effective. However, science is seen to conflict with current religious doctrines in many issues, especially surrounding the sanctity of human life, in all its forms.

Take embryonic research, for example, the scientific rational is that human embryos are the source of stem cells that have the ability to develop into any form of human tissue. This type of research is required to further scientific understanding by creating cell lines in order to investigate human disease and its treatment, specifically where stem cells could regenerate lost tissue.  Embryonic research could be socially beneficial, especially to those who may have need for tissue replacement as a consequence of spinal injuries or organ damage. Replacing this tissue with the patients own would resolve problems associated with rejection, resolving the need for an individual to take immuno suppressant drugs for the rest of their lives.

In the UK, only recently, in 2002, has it become legally permitted to clone human embryos. Surprisingly, according to a survey conducted by the Economic and Social Research Council (ESRC), many people are unaware that human embryonic cloning has now been given legal sanction. From those surveyed only 25 per cent were aware that it is legal to clone human embryonic cells in Britain whereas 47 per cent believed it was illegal. The majority of people believed that the government would not possibly sanction this kind of controversial research.

Government and charity-funded bodies are largely responsible for financing the scientific research that occurs in the UK. Scientific proposals are submitted to these organisations, it is then refereed and scrutinised by a board of experts. If it meets the criteria proposed by the board it becomes funded. Fortunately, research that is unethical or thought to be of a poor standard does not survive this procedure. Generally speaking, controversies in embryonic research are therefore unlikely to occur.

The moral objectives to embryonic cloning are in regards to the destruction of embryos as they have the potential to develop into humans. In addition, there may be the temptation to create genetically manipulated foetuses. The Church and Society Council objected to some  proposals on ethical grounds. They were in agreement that embryos surplus to in vitro fertilisation could be used for stem cell treatment providing this remains within a 14 day limit but were opposed to the deliberate creation of embryos for research or to create cell lines to treat disease. They were also against the creation of genetically manipulated embryos, such as parthenogenetic human embryos, human-animal hybrids, chimeric embryos and human embryos that have been made non-viable. Their main arguments were relating to the long-term uncertainty of such experiments and the lack of ethical controls. Nearly all of these procedures, however, are permitted in the embryos of model animals. Ethical human rights are not extended to other animals in the same way.

Genetically engineered mice expressing Green Fluorescent Protein (Moen et al., 2012. BMC Cancer, 12:21)

It seems likely though, that in the future ordinary cells may be manipulated to behave like stem cells and therefore it is possible that future research would involve very little, if any, embryonic cloning consequently preventing the need to address the ethical issues.

When considering the arguments against human cloning on religious grounds there seems to be an consensus that these advances in science would not be considered in the Bible. Curiously however, and as mentioned in a previous post, the book of Genesis [2.21] describes a process not dissimilar to human cloning, whereby God creates a female human from a man’s rib. Somatic or stem cells derived from skeletal tissue are used to create another being that would be genetically identical. Therefore, perhaps, rather than denounce human cloning the Bible portrays the process as a crucial element to continue human life on earth.

Was God the first molecular biologist?

[The Leaven –  exploring the relationship between science and religion (cont)]

The advent of personal computers, in the 1980s, allowed science to move at an accelerated pace. Answers are now virtually received before the questions are even asked. Research moved at a comparatively slower pace in the earlier part of last century.

In the 1940s, scientists knew vaguely that chromosomes consisted of protein and DNA but at first assumed that proteins transferred hereditary information and that DNA had a structural role merely to provide a framework for the cell and these proteins. This view was overturned when Avery and co-workers discovered that purified DNA taken from infectious bacterial cells could be transferred into non-infectious cells in turn rendering them also infectious. In 1952, Hershey and Chase reinforced this finding by devising an experiment that distinguished the DNA molecule from those of protein. This was achieved by labelling the different molecules with radioactive isotopes and then determining which component was actually transferred into bacterial cells by measuring the radioactivity.

Following this initial research, the importance of DNA was becoming realised and the interest in the molecule surged. In 1953, Watson and Crick deduced the structure of DNA from an X-ray diffraction photograph made by Rosalind Franklin. In a paper published in Nature, they proposed that the DNA molecule was a double-stranded helix and that its replication was semi-conservative with one strand behaving as a template to give rise to an identical daughter strand. These discoveries have been reinforced by further research and have resulted in the complete characterisation of the DNA molecule. The central dogma of molecular biology proposed by Francis Crick was that DNA contained a genetic code organised into genes that was deciphered into proteins by ribonucleic acid (RNA).

Subsequent advances in genetic research have led to a fairly sound understanding into how hereditary functions at the molecular level. Based on much of this knowledge, humans now possess the ability to create a living being, albeit, in a far less elegant way than nature could perform a similar task. Cloning, previously a fantasy in science fiction novels became reality when in the mid 1990s the public were introduced to Dolly the sheep; a clone produced from the genetic material of an adult cell inserted into an empty ova. The cloning of mice and cows was soon to follow, making the ability to clone humans, with all its controversial implications, a very plausible event. In the Bible, it is clear that only God could create a human being in this way. In a process hauntingly similar to cloning, Eve was created by God from Adam’s rib.

Then the Lord God made the man fall into a deep sleep and while he was sleeping he took out one of the man’s ribs and closed up the flesh. He formed a women out of the rib and brought her to him.

[Genesis 2.21]

Cloning continues to be an explosive issue that creates conflict between religious and scientific communities. Perhaps, because science is not currently in a position to provide answers to all the questions that are being asked.