Scientists have discovered a surprising link between Alzheimer’s disease and mad cow disease. It turns out that both diseases involve common protein called prion.

The finding, which appears in the journal Nature, could explain the great mysteries in Alzheimer’s disease: how brain damaging plaques are formed and spread in patient’s brain. The answer to this question could point the way to new treatments for the disease.

In mad cow disease, and a similar human condition called Creutzfeldt-Jakob disease, prion proteins fold into an abnormal shape that appears to cause degeneration of the brain and spinal cord. Mad cow disease can be transmitted by eating the brain or spinal cord of a sick animal.

In Alzheimer’s, prion proteins appear to play a different role. There’s no evidence that prions fold into an abnormal shape or actually cause Alzheimer’s. Instead, they seem to stick to early stage plaques in the brain. These plaques enlarge and appear to damage brain cells.

After screening hundreds of thousands of molecules that occur naturally in the brain, the scientists discovered that the prion protein interacts most efficiently with a protein called amyloid-beta, which is what forms the early plaques in Alzheimer’s.

Scientists confirmed the discovery using mouse models. If prion proteins work the same way in people as in mice, the new research could lead to a drug that would prevent Alzheimer’s by keeping prion proteins from interacting with amyloid-beta.

Dopamine is a neurotransmitter that helps control the brain’s reward and pleasure centers. It helps to regulate movement and emotional responses and enables people to see rewards and work towards them. Parkinson’s disease is caused by dopamine deficiency and using medication to increase dopamine levels in the brain is one of the most popular kinds of therapy.

Italian researchers studied 36 patients with Parkinson’s disease and compared them with 36 healthy controls without Parkinson’s. None of the patients had engaged in artistic hobbies before they took dopamine.

Some Parkinson’s disease patients suddenly became highly creative after dopamine therapy, producing paintings, sculptures, novels and poetry. Thee newly developed interests became so overwhelming in some patients that they ignored other aspects of their everyday life, such as daily chores and social activities, according to research published in the March issue of the European Journal of Neurology.

Researchers have noted that high creative drive has been observed in patients who already have other neurodegenerative diseases or have had a stroke. Authors admitted that it is difficult to identify the anatomical brain regions and physiological processes involved in the creativity effect of dopamine.

Some of the key findings of the study:

The artwork presented by the patients was mainly drawings/paintings (83%), poetry/novels (50%) and sculpture (28%). In 78% of cases, the patients showed more than one skill, normally writing plus painting or drawing.
Some of the patients produced relatively high quality art that was sold and books that were published, but, at the other end of the scale, some of the creative work was of a very poor quality.

The authors believe that the desire to be creative could represent emerging innate skills, possibly linked to repetitive and reward-seeking behaviors. Further studies are needed to support these preliminary observations.

To anyone who accepts Darwin’s theory of natural selection, evolution of sexual reproduction is one of the most puzzling issues. Faster evolution through increasing diversity of genotypes is the obvious long-term advantage of sexual reproduction, but it would seem that the short-term advantages of parthogenesis are so great that ‘sexual’ species would be driven to extinction before the long-term benefits could have an effect.

Parthenogenesis has been observed in dozens of species such as birds, amphibians, insects and fish. This asexual reproduction occurs when an egg cell is triggered to develop as an embryo without the addition of any genetic material from a male sperm cell. Occasionally scientists do find a parthogenetic clone competing with its ancestral sexual species. Usually the clone is found to be steadily outcompeting the ancestral species without strong selective pressure. So why have sexual species survived and prospered?

To give a simplified example, consider a lake populated by a million fish of one species that lives for only one year, and in which fathers do not help raise offspring. Every year, half the fish (the females) lay eggs. For the population to be stable, on average two eggs from each female must be fertilized and successfully reach adulthood.

Now suppose one egg is a mutant. It survives and becomes an adult parthogenetic female. There is no reason to believe that the survival rate of this female’s eggs will be different, so next year there will be two parthogenetic females, genetically identical to their mother, or in other words the beginning of a clone.

Just to keep the arithmetic simple, let us make the unlikely assumption that the lake expands just quickly enough to keep the number of sexually reproducing fish constant at one million. Under these circumstances, the number of parthogenetic fish will double every year. After about twenty years, there will be one million parthogenetic fish, the same as the number of sexual fish.

To continue our arithmetically simplifying assumptions, let the lake shrink at just the rate required to increase competition to the point that on average only one egg from each female fish survives. Now the number of parthogenetic fish will stay constant, but the number of sexual fish will be cut in half every year, until after another twenty years there is only one sexual fish and the lake has returned to its original size. At this point, the sexual species is doomed.

If the size of the lake remained constant, or changed randomly, the proportion of parthogenetic fish would be the same, and so the same result would be achieved. For a larger population, more generations would be needed to eliminate sex, but this analysis would seem to indicate that all sexual species are doomed within a few hundred generations of a viable parthogenetic mutant appearing. Yet sexual reproduction has continued to thrive for at least two billion years. Some other factor must be present.

In our above example, sexual reproduction would seem to disappear after forty years. Whatever factor causes sex to survive must efficiently destroy clones. What factor can be so powerful?

One of the factors that can eliminate clones with such efficiency is disease. That is when the sexual reproduction and associated with it diversity helps population to survive. Let us focus on a disease caused by deadly bacteria. Bacteria divide (parthogenetically, by the way) two or three times an hour, so during the course of a year, or one fish generation, these bacteria would duplicate 25,000 times. Each time a bacterium divides, it introduces DNA mutations because bacteria copy their DNA less accurately than higher organisms.

While the bacteria are infecting a single fish, most mutations will be disadvantageous (i.e. the mutated bacterium will either fail to reproduce, or will reproduce more slowly) but there will be an occasional beneficial mutation that will actually speed up reproduction in the specific environment of that individual fish. If it takes a month for an infection to kill a fish, that is approximately 2,000 bacterial generations. If there is a beneficial mutation every 200 generations, then by the time the fish dies, the most rapidly reproducing bacteria will have accumulated ten mutations helping them prosper in that particular fish.

To outlast the individual fish, the bacteria must have the capability of leaving that individual and infecting another. In a sexual species, the bacterium with ten mutations will find itself in a genetically different fish, in which the very mutations that helped it in its prior home may now be an impediment to survival and reproduction. Before the bacteria manage to shed these mutations and adjust themselves to this new environment, the fish’s immune system may destroy them. If both fish are members of the same clone, on the other hand, the bacterium entering the new fish will find itself in exactly the same environment as it previously prospered in, and should have no difficulty in multiplying rapidly and ultimately killing this fish.

The more numerous the clone becomes, the higher the concentration of bacteria specifically bred to infect and destroy them. It seems almost inevitable that the clone will be completely eliminated well within the 40 years (one million bacterial generations) that it would otherwise take for the clone to destroy the ancestral sexual species.

Problem solved. Sex is here to stay. Perhaps, we should be grateful to bacteria and pathogens for having pleasures of sex and for love in general!

Objective:
Explain the processes involved in cloning and producing transgenic animals

Genetic modification
Genetic modification is the change of the genes of a living organism such as a plant or animal using modern techniques of biotechnology. DNA sequencing of entire genomes has been instrumental in the development of new genetically modified animals.

Purpose of genetic modification of animals
The main purposes of using genetic modification of animals are:

improving food-producing animals and agricultural plants
Development of new of plants and animals through natural selection and evolution is a slow process that takes millions of years. Ancient people learned to improve the speed through artificial selection. As the demand for food increases with world’s population growing, genetic modification of animals and plants became the most efficient way of increasing agricultural production. Genetically modified animals and plants developed in a matter of a few decades produce more and better milk, meat, fiber, they became more resistant to diseases and droughts.

development of treatments for human disease
With genetic modification of animals, production of certain important human proteins such as insulin has become a reality. Scientists have seen success with the use of some animal tissues, bones, and joints in humans. Research continues in the field of skin and organ tissue transplantations. Pigs are commonly used in this research because of their similarities to humans. Pigs producing ‘humanized’ skin, for example, can be used as a source for skin restoration in humans. Animals such as mice are genetically modified to help understanding and developing treatments for human and animal diseases.

production of pharmaceuticals
Genetic engineering has allowed production of certain hormones (insulin, human growth hormone, bovine and porcine somatotropin and other). Current research has shown the possibility of genetically modifying sheep or cattle to produce human proteins in their milk.

Benefits
Genetic modification of animals has shown several benefits. These include increased resistance to disease and parasites, increased productivity and improved hardiness to weather factors. Other benefits involve animal products, such as increased yields of meat, eggs, and milk.

Cloning animals
There are two main types of animal cloning: reproductive cloning and cloning through recombinant DNA technology

Reproductive cloning is a common process very well known for creating an exact genetic match of an animal. In 1996, Dolly the sheep was produced by reproductive cloning and was the first animal to be cloned from adult DNA. Since Dolly, advancements have been made in the process of cloning, and several other animals have been cloned. The reproductive cloning process begins with the transfer of genetic material from the nucleus of a donor adult cell to an egg whose nucleus has been removed. The egg is stimulated with chemicals or electrical current to promote cell division. As the cloned embryo divides in a test tube and reaches a suitable developmental stage, it is transplanted into a female host. The female carries the cloned embryo until birth.

Recombinant DNA (rDNA) technology is the process that occurs when fragments of DNA from two different species are joined in vitro to form a single DNA molecule. Usually, the DNA from one species is incorporated in a plasmid that is a circular DNA replicating independently on the bacterial genomic DNA. A plasmid is then amplified inside the bacteria, isolated and inserted into the genome of embryonic stem (ES) cells to be altered, allowing the DNA of two different organisms to be combined in a single cell. Then the cell is injected into an embryo at early stage of development and the embryo is then implanted in foster mother uterus to produce a chimeric transgenic animal.

Transgenic animals
A transgenic animal is an animal that has incorporated a foreign gene into its cells. The animal can pass this transgene (altered gene) on to its offspring. Every cell within the transgenic animal contains a copy of this transgene. Several different methods can be used to produce transgenic animals.

Microinjection is the most common technique used to produce transgenic animals. Injecting DNA into a cell using a fine-diameter glass needle and a microscope constitutes microinjection. During this operation, the chosen gene from the same or a different species is directly microinjected into the ovum. The injected DNA integrates randomly with nuclear DNA and its expression is possible only when the foreign DNA is attached to a suitable promoter DNA sequence. There are many examples where different types of animal cells have been microinjected and successfully transferred.

Once a manipulated fertilized ovum develops to a specific embryonic phase, it is transferred to the oviduct of a recipient female. The embryo will develop just as a normal embryo and is typically carried full term.

Marker gene is a gene that helps easily identify animals which successfully incorporated transgene. With the use of marker genes, it is possible not only to determine whether a transgenic animal has received the desired DNA but also whether the genes in the DNA are being expressed. The genetic markers help identifying the location of incorporated DNA in the host genome. The expression of a marker gene can be visualised with staining selected tissues or whole embryos. Polymerase chain reaction (PCR) followed by gel electrophoresis is a technique of choice due to its speed and sensitivity.

Improving domestic animals
Currently the U.S. Meat Animal Research Center (USMARC) has developed DNA markers to identify all cattle in the United States. This method allows improved animal traceability and verification of disease sources. DNA testing also allows producers to base their management and selection process on genetic potential of identified animals.

DNA testing can determine the presence of certain traits and proteins. A common method used in the beef cattle industry involves the presence of the tenderness or marbling genes. This information allows producers to enhance the production of tender meat and meat with optimal marbling. It also allows producers to produce a consistent product.

Xenotransplantation
Xenotransplantation is the transfer of living cells, tissues, or whole organs from one species to another. People who need a kidney for transplantation often chose to use a pig kidney even if that organ was obtained from a genetically engineered pig.

Summary:
With the new technology of genome sequencing and mapping, genetic modification holds the potential for improvements in livestock. The main purposes for using genetic modification of animals are increased production of food-producing animals, treatments for human disease, and production of pharmaceuticals.

Did you know?
1. Identical twins are clones that occurred naturally.
2. Many animal cloning technologies are used for clinical reproductive procedures.
3. The process of cloning in the lab is a very complex procedure.

Checking what you have learned
1. What are the main purposes of genetic modification in animals?
2. What is a transgenic animal?
3. What are the steps involved in cloning an animal through reproductive cloning?
4. What are the steps involved in producing a transgenic animal?
5. How are marker genes used?

Stem cells are unique cells that are able to convert into any cell type. Stem cells play a vital role in developing, maintaining and repairing these tissues. There are two main types of stem cells, embryonic stem cells, present in the embryo and adult stem cells which can be found in all organs and tissues of adult organism. Embryonic stem cells are capable of differentiating into any specialized cells in the body, while adult stem cells are able to differentiate into mature cells of a particular type.

Probably, the greatest potential for stem cells is in their use to treat degenerative diseases and major traumatic injuries, which may result in a significant improvement in the quality and length of life for affected patients. Stem cells could be developed into healthy versions of the cells that have been lost or that are not functioning correctly in that particular disease or condition. These stem cells would then serve as renewable sources for the cells and tissue needed for transplantation into patients. The ability to replace defective or damaged cells through cell replacement therapy could allow the treatment of injuries and various genetic and degenerative conditions. The list of diseases that may be good candidates for stem cell repair include muscular dystrophies, retinal degeneration, Alzheimer’s disease, Parkinson’s disease, arthritis, diabetes, spinal cord injuries, and blood disorders such as hemophilia, but many other diseases may turn out to be excellent targets as well. Recently, cloning techniques have been developed that allow scientists to develop stem cells that can be used to better understand specific diseases with the goal of using this knowledge to develop better treatments for those diseases. In the groundbreaking procedure, called “nuclear transfer,” the genetic material (DNA) of an unfertilized egg is removed and replaced with the genetic material from a single skin cell of a patient with a severe disease to permit the generation of stem cells for further study of the disease.

This cloning method was used to create the famous sheep Dolly in 1996. Experts believe that with this technique, they are able to create cells, organs, tissues, which will be used to treat patients. If so, organs for transplantation will be readily available and it will become possible to cure many diseases, save and prolong lives of many people.

In vitro fertilization (IVF) is a common treatment option for many couples seeking relief from infertility. In this case, conception, or fertilization of an egg (oocyte) with a spermatozoa takes place in a test tube in laboratory settings and the resulting fertilized oocyte is then implanted after a few cell cycles in the uterus. It is a standard practice in fertility clinics to fertilize and cryopreserve more eggs than women are willing to carry to term. Most couples who have surplus of frozen embryos choose to discard them after completing their family, but many couples do not feel comfortable with this option and instead choose to donate them to stem cell research so that these embryos can be utilized to help others. Fertility centers then provide these fertilized human eggs to stem cell research laboratories where embryonic stem cells are isolated from these embryos cultured for approximately a week. These stem cells continue to grow in vitro and divide for long periods of time and are used for further studies such as production of specialized human cells and tissues. For example, a scientist might place the stem cells in conditions that cause them to form neural (brain) cells with the goal of someday using them as a source of cells to treat Alzheimer’s disease. Sheets of artificial skin may be produced from embryonic stem cells and used to treat severe burns.