Leaven in a molecular era.

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

Not only does yeast now serve as one of the most important organisms throughout domestic history, in recent years it has also substantially contributed to biological research. The numerous molecular techniques that have evolved in yeast have allowed it to make an important contribution to a number of areas in science. Through studying various types of yeast and other microbes, scientists now know a great deal about the molecular processes involved in cell division, rapid evolution and disease.

Fortunately, individuals with skin diseases are no longer thought of as unclean and are normally treated within the community. Scientists have greater understanding of disease management and although quarantine and hygiene are still practiced they are now carried out in order to reduce disease transmission. In the majority of cases, people are not ostracised when they are infected by disease, although fears and anxieties can still be generated through sensational media coverage. Nevertheless, even in this molecular age, some transmissible diseases are still associated with sins of the flesh and can lead to social ostracisation.

Yeast colonies in an array. Each spot contains thousands of yeast cells. The plate shows synthetic lethal interactions when the interaction of 2 or more genes cause cell death (shown by colonies with reduced/no growth colonies). Image uploaded by Masur

There are still many diseases that generate fear because they are untreatable. Some of these have evolved through human activities, such as Bovine spongiform encepthalopathy (BSE) which gives rise to a human form of spongiform encepthalopathy called variant Creutzfeldt-Jakob Disease (CJD). The causative agent of BSE is a defective version of a protein called prion that is similar to one found in the brains of sheep with Scrapies. The prion protein is transmitted horizontically and causes disease through disrupting the normal function of the native protein. Studying the molecular mechanisms by which proteins change conformation to become prions in yeast has led to a greater understanding in the pathology of this disease. Many other human diseases, especially cancers, can be researched by studying molecular processes first in yeast.

Cancers arise when cells begin to divide abnormally due to mutations in DNA. Cancer research investigates the mechanisms that encourage these mutations to arise. The mechanism of cell division is often studied in fission yeast, Schizosaccharomyces pombe. Unlike Saccharomyces cerevisiae, which divides by budding, S. pombe divides symmetrically in a similar way to human cells. Fission yeast originates from Africa were it is found growing on banana skins and is used to ferment beer. Through research in this area scientists have reached many milestones in the mechanisms that have caused various cancers leading to greatly improved clinical treatments. Work yeast genetics has greatly contributed to our understanding of cell cycle research and has led to the award of a Nobel prize in 2001 to three scientists who led pioneering work in this area: Paul Nurse, for his work in S. pombe and human model systems; Leland Hartwell, for his work in S. cerevisiae; and Tim Hunt who used sea urchins as a model system. Researchers later found similar cell division genes in human genomes.

Scanning electron micrographs of Fission yeast (Schizosaccharomyces pombe). Image by David O Morgan.

In addition to investigating diseases, yeast is also used as a model system to research ageing. Saccharomyces cells can divide by budding a number of times but the new bud is always physiologically younger than the mother cell. Each cell produces about thirty buds depending on the environmental conditions and other factors. About thirty genes in yeast have already been found to be involved in ageing. The main factors seem to be related to metabolic capacity, resistance to stress, gene dysregulation and genetic stability. Encountering certain environments that would overload any of these factors would also affect longevity. For instance, excessive oxidative damage or radioactivity would lead to a high level of mutations that will reduce the number of times that a cell can bud. Excessive oxidation is associated with the consumption of calories; so caloric restriction should result in increased longevity. This has been demonstrated in yeast, limiting the amount of nutrients and carbohydrates available in growth medium leads to a longer generation time and life span.

…give us this day our Showbread

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

It becomes apparent while reading the Bible, that bread is an important part of Hebrew life and was frequently allied to rituals and ceremonies. Moses is instructed through God to always leave an offering of bread in the presence of the Lord. Precise instructions were given to Moses on how a table for serving the bread offering should be made:

Make a table out of Acacia-wood, 2 units long, 1 unit wide, and 1.5 units high. Cover it with pure gold and put a gold border around it. Make a rim round it and a gold border around the rim. Make four carrying-rings of gold for it and put them at the four corners, were the legs are. The rings to hold the poles for carrying the table article are to be placed near the rim. Make the poles of Acacia-wood and cover them with gold. Make plates, cups, jar and bowls to be used for wine-offerings. All of these are to be made of pure gold. The table is to be placed in front of the Covenant Box, and on the table there is always to be the sacred bread offered to me.
[Ex. 37. 10-16]

Perhaps this precision offered some kind of order to the Hebrews in what was an otherwise unpredictable life. The bread that was displayed on this table was called Showbread or Bread of the Presence. There were very specific and precise instructions on how this bread should be placed on the table:

Take twelve units of flour and bake twelve loaves of bread. Put the loaves in two rows, six in each row, on the table covered with pure gold, which is in the Lord’s presence. Put some frankincense on each row, as a token food-offering to the Lord to take the place of the bread. Every Sabbath, for all time to come, the bread must be placed in the presence of the Lord. This is Israel’s duty forever. The bread belongs to Aaron and his descendants, and they shall eat it in a holy place, because this is a very holy part of the food offered to the Lord for the priests.
[Lev. 24. 4-9]

The twelve loaves of Showbread are thought to represent the twelve tribes of  Israel. The loaves were changed every Sabbath, then eaten by the priests who replaced it. The bread used would have been unleaven as  leaven was regarded as an impurity and it may indeed have contained pathogenic microbes. It would not be implausible to suppose that ritualistic ceremonies that excluded leaven, like this and the Passover, inadvertently offered protection from disease thereby giving the impression that a supernatural power had spared the worshippers.

Twelve loaves of Showbread and two cups of frankincense displayed on a golden table until the Sabbath. Image by Ori229

No grain offerings presented to the Lord were permitted to contain leaven, but must contain salt, perhaps because its preservation qualities may have prevented contamination  from taking place, by inhibiting the growth of microbes:

None of the oblations that you offer to the Lord is to be prepared with leaven, for you must never burn leaven or honey as an offering to the Lord. You may offer them up to the Lord as an offering of first-fruits, but they must not go as an appeasing fragrance at the altar. You must salt every oblation that you offer, and you must never fail to put on your oblation the salt of the Covenant with you God.
[Lev 2.13]

This regulation also applied to grain when it was given as part of a sin offering [Lev 6.17] and when Aaron ordained his sons as priests, the consecration offering was bread made without leaven [Ex 29.2]. In the book of Numbers the ceremony to become a Nazarite involved a complicated ritual of animal sacrifice and head shaving in addition to an offering of unleavened bread:

When a Nazirite completes his vows, he shall perform a ritual. He shall go to the entrance of the Tent and present to the Lord three animals without any defects: one-year-old male lamb for a burnt offering, a one-year-old ewe lamb for a sin offering and a ram for a fellowship offering. He shall also offer a basket of bread made without leaven.
[Num 6.13-15]

Although leaven was not permitted in sacrifices to the Lord it was allowed in thanksgiving celebrations in appreciation of the Lord’s many blessings. In this ritual the food was shared amongst the offerers and leaven was often added perhaps to symbolise the expanse of the harvest. The Harvest festival was performed to celebrate the first harvests of corn as a kind of thanksgiving ceremony:

You must bring from your houses to present with the gesture of offering- two loaves, made of two-tenths of wheaten flour baked with leaven, theses are first-fruits for the Lord.
[Lev. 23.17-18]

The authoritative and God-fearing message presented by the Old Testament is in sharp contrast with the philosophies of the New Testament. The Old Testament clearly states that if the Torah is disobeyed serious repercussions will occur. Following the Torah may have had beneficial affects in an era before antibiotics and vaccinations revolutionised disease control. These doctrines would also protect a community from diseases that have no known treatment or vaccine. Currently controlling microbial contamination and disease still preoccupies society but is no longer shrouded in mystery as in the past. Immunisation is now so commonplace, that disease in the 21st century is generally less feared than in the Biblical era, when life expectancy was rarely above thirty-five years.

In addition to transmitted diseases there were also many environmental and incidental health concerns like silicosis from breathing sand, the development of tetanus from infected wounds, conditions caused by malnutrition such as osteopetrosiscongenital diseases and malignant tumours. Some of these conditions such as malignant tumours and congenital diseases occur to this day and are still the subject of scientific research. The difference being that these diseases are not contagious  obviously would not have had the same social impact as those caused by transmissible pathogenic microbes. The symbolic portrayal of leaven as a sign of permeating corruption in the Old Testament seems an accurate interpretation of what the Hebrew society most feared at the time, the threat of disease through contamination by microbes.

…how to avoid the Destroyer

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

During the Passover, Moses claimed that the Lord would ensure that every first born in Egypt would die at midnight.  The Passover was an ancient ceremony practised uniquely by the Hebrews, and not  the Egyptians. It was a ritual  practiced by shepherds, at the first full moon of spring, to ward off evil spirits in order to protect lambs and goats during birth. This explains the logic behind the species chosen as the sacrificial beast, either a young sheep or a goat. They believed the evil spirits would kill newly born animals. If the blood of a sacrificed animal was smeared on to door posts it would keep away the Destroyer. The Destroyer was most likely to be the bringer of disease or plagues. The ovine meat was later eaten during a nocturnal family festival and may have included herbs to enhance the smell and make it pleasing to the deity concerned. This is another way by which the community dealt with uncertainty. They did not understand the epidemiology of disease or the causative agents and therefore attributed stillbirths to the retaliation of an angry supernatural being.

A lamb prepared for sacrifice. Josefa de Ayala c1670s

The following paragraphs explain how the Passover had been modified by Moses to prepare for the Exodus. It describes how the sacrificial blood spread on the doors would be used by the Lord to distinguish Hebrew houses from those of the Egyptians:

 The Lord spoke to Moses and Aaron in the land of Egypt: “This month is to be the first month of all the others for you, the first month of your year. Speak to the whole community of Israel and say: On the tenth day of this month each man must choose either a lamb or a young goat for his household. If his family is too small to eat a whole animal, he and his next-door neighbour may share an animal, in proportion to the number of people and the amount that each person can eat. You may choose either a sheep or a goat but it must be a one-year-old male without any defects. Then, on the evening of the fourteenth day of the month, the whole community of Israel will kill the animals. The people are to take a sprig of hyssop, dip it into the bowl containing the animals blood and strike the doorposts and above the doors of the houses in which the animals are to be eaten. That night the meat is to be roasted, and eaten with bitter herbs and unleavened bread. Do not eat any of it raw or boiled, but eat it roasted whole, including the head, the legs, and the internal organs. You must not leave any of it until the morning; if any is left over it must be burnt. You are to eat it quickly, for you are to be dressed for travel, with your sandals on your feet and your stick in your hand. It is the Passover Festival to honour me, the Lord.”

“On that night I will go through the land of Egypt, killing every first-born male, both human and animal, and punishing all the gods of Egypt. I am the Lord. The blood on the doorposts will be a sign to mark the houses in which you live. And when I see the blood, I will pass over you; and you shall escape the destroying plague when I strike the land of Egypt. You must celebrate this day as a religious festival to remind you of what I, the Lord, have done. Celebrate it for all time to come.”
[Ex. 12, 1-20]

It is evident that the Hebrews continued eating unleavened bread when they left Rameses heading for Sukkoth, as they had no time to put leaven back into their dough:

The Israelites set out on foot from Rameses for Sukkoth. There were about 600,000 men, not counting women and children. A large number of other people and many sheep, goats and cattle also went with them. They baked unleavened bread from the dough that they had brought out of Egypt, for they had been driven out of Egypt so suddenly that they did not have time to get their food ready to prepared leavened dough.
[Ex. 12.37-39]

In an address by Moses to the Hebrews, after the exodus, he stated that the day they left Egypt was to be commemorated by the festival of unleavened bread to remind them of the haste with which they departed, having no time to put leaven in their dough.  The festival of unleavened bread traditionally occurred the day after the Passover:

The Lord said, “For seven days you must not eat any bread made with leaven- eat only unleavened bread. On the first day you are to get rid of all the leaven in your houses, for if anyone during those seven days eats bread made with leaven, he should no longer be considered one of my people. On the first day and again on the seventh day you are to meet for worship. No work is to be done on these days but you may prepare food. Keep this festival, because it was on this day that I brought your tribes out of Egypt. For all time to come you must celebrate this day as a festival. From the evening of the fourteenth day of the first month to the evening of the twenty-first day, you must not eat any bread made with leaven. For seven days no leaven must be found in your houses, for if anyone, native born or foreign, eats bread made with leaven, he shall no longer be considered one of my people. You must eat no leavened bread; wherever you live you must eat unleavened bread.”
[Ex. 12.15-20]

It is interesting that at the time diseases and plagues were spreading through the Nile Delta area the Hebrews abstained from eating leaven. It was a normal practice of the Egyptians to allow the dough from bread to rise in the sun, this would make it a vulnerable target for disease carrying insects that would inevitably lead to the spread of communicable disease. By not eating leavened bread for several days the Hebrews were unwittingly protecting themselves from a potential reservoir of pathogenic organisms. Eating only freshly killed meet in the cooler climate of the evening, then completely burning any leftovers would offer further protection from any contaminating microbes. Perhaps as a consequence of this, and segregation in other social practices, the spread of disease that occurred within the Egyptian population permitted the Hebrews too escape at a time when resistance was weakened.

Bread containing leaven is traditionally burnt before the Jewish Passover. Image by Valley2City.

When the Hebrews left Egypt they continued to treat leaven as an impure substance that could displease God. The removal and burning of leaven is still carried out before Passover in some religions. During the Jewish celebration, it is traditional to hunt for any leaven (also known as Chametz) remaining in the house, the evening before Passover, by candlelight with a wooden spoon and  feather to dust away and scoop up crumbs to be burned the following day. Blood is no longer smeared on door posts though.

…the metabolic habits of microbes have earned them a bad press

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

Based on archaeological evidence, it is thought that the Earth was created approximately 4.6 billion years ago and that life originated in the form of bacteria 3.8 billion years ago. Multicellular organisms, in various microscopic forms, are thought to have first existed about a billion years ago and are thought to have given rise to simple animals,such as sponges and anemones. More complex forms of animals started to appear 550 million years ago (mya). Arthropods are thought to have appeared first, followed by fish, land plants, insects, amphibians, reptiles, mammals, birds and flowering plants respectively. First primates that resembled humans arrived on the scene 2.5 mya with humans resembling the present form arriving just 200,000 years ago. Neanderthals disappeared fairly recently, only 25,000 years ago. A short time in evolutionary terms but still a vast time scale  for a human with an average life span of 62.5 years to visualise. When the Bible was written human life span was only 28 years.

Trilobite fossils, early anthropods that are now extinct. Image Moussa Direct Ltd.

The Bible condenses the time scale that humans arrived on earth within the space of a few days. On the first day God created light which was divided into day and night. The next day, water were divided from the sky and earth was divided into land and sea. It was not until the third day that Life first appeared when God created vegetation. During the fourth day planets and stars were added with time being divided into seasons, days and years. On the fifth day God creates birds and sea creatures,  commanding them to be fruitful and multiply. Finally on the sixth he adds wild beasts, livestock and reptiles, creating humanity in his own “image”. The humans are instructed to be fruitful, multiply, fill the earth and subdue it. In the book of Genesis the Bible draws a distinction between animals and humans, with emphasis on human superiority.

God said, ‘Let us make humans in our own image, in the likeness of ourselves, and let them be masters of the fish of the sea, the birds of heaven, the cattle, all the wild animals and all the creatures that creep along the ground.’
[Gen 1. 26]

There are a number of misconceptions in the account of creation within the Bible. The stars and planets must have existed before the introduction of life.  Seasons would  prerequisite the existance of vegetation. We are now also aware that reptiles existed before mammalian species on account of dinasaur fossil records. These restrictions in knowledge also result in no reference to the creation of microbes within Genesis but there are several references to disease and of fermentation processes throughout the Bible.

An early reptilian Apatosaurus louisae skeleton in the Carnegie Museum. Image by Tadek Kurpaski

Ancient civilisations would be completely unaware of the causes to many diseases. In general, injuries resulting from accidents or animal bites were understood and treated by various dressings, including sesame oil, wine and balsams, some of which contained naturally occurring antibiotics. In contrast the mechanisms behind diseases involving parasites or microbes were a complete mystery and thought to have been placed in the body by evil forces. Consequently, these illnesses were treated by making the body hostile to the invader through intense cleansing with various noxious substances. Diseases were largely viewed as a punishment brought through sin or disobedience.

The Lord said, ‘If you will not obey my commands, you will be punished. If you refuse to obey my laws and commands and break the covenant I have made with you, I will punish you. I will bring disaster on you- incurable diseases and fevers that will make you blind and cause your life to waste away.
[Lev 26.14-16]

As microbes where viewed as some kind of mysterious, unexplained power they were also used to represent the spread of sin and corruption. For instance, in his first letter to the Corinthians, Paul the Apostle uses the permeating character of leaven to illustrate the spreading of corruption within a community.

You know the saying, “A little leaven makes the whole batch of dough rise.” You must remove the old leaven of sin so that you will be entirely pure. Then you will be like a new batch of dough with no leaven, as indeed I know that you actually are. For our Passover Festival is ready, now that Christ, our Passover lamb, has been sacrificed. Let us celebrate our Passover, then, not with bread having the old leaven of sin and wickedness, but with the bread that has no leaven, the bread of purity and truth.
[1 Cor. 5.6-9]

…it’s life, but not as we know it

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

Increased curiosity and the need to obtain better images of microscopic structures eventually led to the development of the light microscope that could magnify specimens up to 1500 times the original size. Visible light that passes through a specimen refracts as it travels through a lens thereby enlarging the final image.

In the 1930s, improved resolutions were obtained by using a stream of electrons instead of light waves; an electron microscope can magnify 1000 times greater than the light microscope. Using these techniques it was possible to visualise viruses so tiny that they were able to infect bacterial cells. Theses viruses were called Bacteriophages. Alien-like particles that can inject their genomes into a host cell. The viral genetic material is replicated by the hosts enzymes to produce hundreds more of the tiny particles. These particles eventually burst out of the cell killing it in the process.

Bacteriophage injecting their genetic contents into a bacterium. Image by Graham Colm.

A single bacteriophage. Image by Hans-Wolfgang Ackermann.

Being able to see images beyond the scope of natural sight has greatly enhanced scientific and medical research. Visualising cell functions has removed the uncertainty that would have obstructed the advancement of many theories and hypotheses. Improvements in microscopy and genetic techniques have revealed that there is far more to the natural world than first imagined. The advent of photography meant that these findings no longer had to remain in the lab or as drawings within books, now an accurate visualisation of experiments and specimens could accompany written diagnoses, thereby increasing the validity of findings.

Additionally, media technology allows immediate access to the scientific results so they can now be distributed internationally. Humans can now see beyond their natural ability and realise that billions of organisms exist in the microscopic biosphere. Additionally, the causative agents of many diseases are no longer a mystery. Yet along with these innovations remained the sinister irony that organisms this tiny could still impose more of a threat to humanity than those with a far greater mass. Humanity has not underestimated this threat, and is slowing winning the war against the threat of extinction through disease. In 1970 WHO announced the complete eradication of the  smallpox virus. Societies no longer had to adopt the extreme behavioural changes stipulated in the Old Testament  in order to avoid the spread of disease.