Pig-human chimeras: a clinical trial announced in Japan

 

    In an article published in 2019 on Bioethics Press Synthesis, Henrianne introduced one of the new advancements in biology and the medical field, but it is also one of the most controversial experiments in recent years. 

    In this era, there is a high demand for organ transplants. In the past, the organs were mostly from human donors. But as science becomes more advanced, we have found ways to use organs from animals to transplant for those in need, rather than waiting for a donor, which is very rare. In 2019, a Japanese researcher, Hiromitsu Nakauchi, announced his new experiment in Japan to culture human pancreas in pigs. This was proposed soon after Japan had relaxed its chimera law. 

    In this experiment, he planned to inject human induced pluripotent stem cells into genetically modified pig embryos. The result after these cells are injected was described as: 

"These iPS cells will take the place of the removed gene in the embryos to create a human pancreas. The chimera embryo will then be implanted into a carrier sow’s uterus. The foetus will be removed before birth to study how much pancreatic tissue is derived from human iPS cells and how it functions." (Pontbriand, 2019). 

This is a big advancement in the study of chimeras. But at this time, these animal-human chimera embryos can only be implanted into animals; implanting chimeric embryos into humans is still prohibited. 

WORKS CITED

Pontbriand, H. D. (2019). Pig-human chimeras: a clinical trial announced in Japan. Bioethics News. https://bioethics-news.com/2019/05/13/pig-human-chimeras-a-clinical-trial-announced-in-japan/

Raposo, V. L. (2021). The new Japanese regulation on human/non-human chimeras: should we worry? National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC7863089/

Genetically Modified Babies

A process known as "mitochondrial manipulation technology" was discussed by the Cellular, Tissue and Gene Therapy Advisory Committee, part of the FDA, in 2014. In general, germ line gene therapy is a highly controversial topic, making research and advances in this field difficult in some areas on the world. For some, they believe that the creation of new life is a sacred process that should not be tampered with. Others point the risks and possibility of devastation if errors are made within humans. In theory, mitochondrial manipulation technologies could make mitochondrial diseases a thing of the past. This technique is especially interesting and controversial because it requires the use of genetic material from three parents in the creation of a child. Because mitochondrial DNA is inherited from the mother, this technique focuses on the transfer of DNA from one egg to another, to provide an egg with healthy mitochondria for the future child. In an informative New York Times article the process is described as one that consists of "removing the nuclear material either from the egg or embryo of a woman with inheritable mitochondrial disease and inserting it into a healthy egg or embryo of a donor whose own nuclear material has been discarded". The article notes that 1,000-4,000 children are born annually with mitochondrial diseases that are potentially devastating and without a cure. Unfortunately, the research done at Oregon Health and Science University raises many questions about the current technology in mitochondrial manipulation. In trials with macaque monkeys, five successful offspring were produced and future research will be done to see how these manipulations will affect future generations. However, in trials with human zygotes, mutations and other developmental abnormalities were seen that were absent from the trials with macaque monkeys. The sensitivity of human embryos makes me wary of the use of this technique until more successful methods are developed. Overall, I think that this is an interesting method for mothers to avoid passing mitochondrial disease to her children. Without further research, I know that it would be impossible to attempt to use this technique to make mitochondrial diseases preventable. Since this discussion, new news on the topic is few and far between. England continued mitochondrial manipulation research and in 2015 they passed a law, allowing fertility clinics to use this technology. With the continued interest in this area of research in Europe, I hope that they can fine tune their mitochondrial manipulation techniques so that they will be safer, more effective and that their success will make skeptics more willing to accept this groundbreaking technology.

Ethics and Embryos

In terms of ethics, studies involving human subjects are constantly questioned. Many people fear the consequences of "designer babies" or unpredictable outcomes of altering DNA in such a complex organism at crucial stages, while others argue the benefits of eliminating dangerous heritable diseases. While the debate of ethics continues in America continues today, April 2016, scientists in China have moved past talking, and into testing the possible benefits of gene editing in human embryos. Nearly a year ago, April 2015, Protein and Cell published a controversial article about a Chinese study led by Junjiu Huang on genetic modification of human embryos. In this study, embryos were injected with an enzyme complex known as CISPR/Cas9, a tool that binds and splices DNA at specific locations. With this technique Huang and his colleagues attempted to edit the HBB gene, which may mutate to cause beta thalassemia. Unfortunately, their experiments was considered unsuccessful for many reasons. Firstly, 71 out of the original 86 embryos survived the first 48 hours after injection. Of the 71 surviving embryos, most were tested and a mere 28 had been successfully spliced. The experiment was halted with such a low success rate, and unexpectedly numerous additional mutations.

 An article published in Nature's news section noted that Huang's study was rejected for publications by both Nature and Science magazines due to the great question of ethics. Throughout the articles I have found, I am definitely curious about the ethics of this study too. While the experiment is clear, I have many questions about the before and after details of the study, as I imagine that many people within this ethical debate do. In the Nature article, there were multiple times in which the use of "abnormal" embryos and avoidance of "normal" embryos in these types of studies were mentions. What makes the embryo normal or abnormal?  Where do the embryos come from and what happens to them after the study? While I think that genetic modifications of human embryos could be an important technique to eliminating genetically coded issues such as diseases, it is a very difficult and risky task due to the numerous issues of ethics brought to light within this research. 

Engineers Gain Control of Gene Activity

Charles Gersbach

Researchers at Duke University in North Carolina have developed a new technology to manipulate proteins that package our DNA, and by doing so are able to turn on specific gene promoters and enhancers - DNA sequences that influence the activity of their corresponding genes. The ability to do this allows for control of gene activity. The combination of all molecules responsible for the activity of genes in the genome is known as the epigenome, and is the main subject of attention for this current research. The ability to alter the actions of the epigenome allows researchers to see what roles the promoters and enhancers play in many biological contexts, including cell fate, risk of diseases, and stem cell research.

Assistant professor of biostatistics and bioinformatics at Duke University Timothy Reddy teamed up with Charles Gersbach to modify the previously established system called CRISPR to alter DNA packaging at specific sites. This process allowed not only for activation of gene promoters but also for the activation of adjacent genes. The developed method has worked better at accomplishing this task than other methods previously tried.

The true benefit to this research is the effect it may have on understanding and diagnosing modern day diseases such as neurodegenerative conditions and cancer. Many diseases are quite complex genetically, as there may be many enhancers and/or promoters that affect the activation of genes that cause the expression of a disease. Being able to isolate these enhancers and promoters in the epigenome may provide paramount insight into the treatment of modern diseases.

The largest producer of Genetically modified food=America

                                                                       Almost 70% of the foods at the grocery stores are genetically modified. The most common are soybeans, cotton and maize. Therefore any foods that contain corn syrup such as cereal, snacks and soda are genetically modified. America is the largest producer of genetically modified crops. Genetically modified food is also known as biotech or genetically engineered food. These foods are plants that are modified in the laboratory to improve desired traits.

         When a plant is genetically modified, a foreign gene in inserted in the plants own genes. For example, a gene resistance to pesticides. It is possible to transfer genes to other plants with genetic modification because genes are created from the same material. There are four main steps to genetics modification. One- the scientist finds and isolates the desired genetic characteristics. Two- several copies of the isolated gene are made. Three- the desired genes are transferred to the plants genes by a transformation method. Four- From the genetically modified plant tissue, a new plant is made

. Anything that lives can be genetically modified, but not all characteristics can be transferred.

        There are many pros and cons for genetic modified food. The most important pro is that it can produce plants that are more resistance to pest and diseases. Other benefits are faster growth, more nutritious crops, better tasting foods and production of medicines by crops. The most important con to genetically modified foods is the unexpected side effects on human health. Other cons are ecological damage, reduced species diversity, over-use of herbicides and effects on non-GM crops. 

Link One: http://www.nlm.nih.gov/medlineplus/ency/article/002432.htm

Related Link: http://learn.genetics.utah.edu/content/science/gmfoods/

A New Effective Method of Genome-Editing

Research and technology in genetic modification and genome-editing is a contemporary field that is broadening its horizons at an exponential rate. Genome-editing often relies on the technique known as CRISPR/Cas9. This processes relies on two key tools of gene insertion. The first of which being an endonuclease enzyme to cut the DNA at specific points designated by the researcher. The second tool for CRISPR/Cas9 is the use of a promoter (a promoter is an on switch to turn on a designated gene). This process has been used by researchers to insert genes and to disable genes at the researcher's control. However, using this method in humans is risky. The use of a Cas9 to cut DNA at specific locations could also cut DNA at unintended locations, and the use of a promoter could also effect unintended genes.

A new method was tested and developed by the Stanford University Medical Center led by Mark Kay and Adi Barzel. The goal of their testing was to not only eliminate the use of nucleases and promoters for gene insertion, but to also cure hemophilia in mice. To do this they used a modified virus that was removed of all viral DNA and left only therapeutic DNA containing a blood clotting factor gene. This was inserted into mice and targeted the albumin gene. They then relied on genetic recombination of chromosomes to copy the genes inserted into the mice. They were able to cure hemophilia in both newborn and adult mice with the inserted blood clotting factor gene. This is revolutionary in that not only were they successful in curing a disease that effects human's worldwide, but also it eliminates the risk of the old method of gene insertion. Much more work, research, and testing must be done on the new method, but the future of gene therapy in humans is looking promising.

Article Link: http://www.sciencedaily.com/releases/2014/10/141029145444.htm
Supporting Link:http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13864.html

Babies Modified Genetically

Marcy Darnovsky in this article discusses the biological procedure of creating genetically modified human beings. The procedure is called mitochondrial manipulation by the FDA. The process of this procedure starts by surgically removing the nuclear material from the affected woman's egg or embryo of the mitochondrial disease. The egg or embryo in the woman must have the inheritable mitochondrial disease initially before the process can be done to be replaced with the new healthy egg. The mitochondrial disease affects an estimated one-thousand to four-thousand United States children. The disease is from a genetic abnormality with defects of converting food into energy, and can also be caused by exposure toxins. The disease can only be passed down from the mother of the offspring, and the procedure of manipulating the mitochondrial will potentially aid in allowing these affected women to give births to unaffected children in the future. I think that this discovery is noninvasive and can have the potential to eliminate the carriers of the mitochondrial disease throughout the generations of the future. The fact that with each procedure removes the risk of the mother's offspring from passing on the disease, this would result in the child not passing it onto their future offspring which is ideal for the elimination of the mitochondrial disease thriving.

Using Bacillus thuringiensis to replace standard pesticides for crops

Farmers have long dealt with the struggle of losing their crops to ravenous insects and being forced to use pesticides to protect their harvest. The problem with many of these pesticides is that they are broad-range type pesticides meaning that if a farmer sprays this pesticide to kill a specific beetle, that the poison will kill the beetle but may also kill any other insects exposed whether they are beneficial or not. These pesticides are also often harmful to other species including mammals, fish, and birds. In same locations, the level of pesticides applied to the crops to keeps the insects away is well over the regulated amount that is safe for consumption. Not to mention the cost of the pesticides and the cost of fuel to have the pesticides spread around. To combat this problem, scientists have been looking into the idea of modifying certain crops to utilize the bacterium  Bacillus thuringiensis.



Bacillus thuringiensis (Bt) is a common soil bacterium that produces produces poisonous proteins. The scientists singled out the toxin-making gene from the bacterium and could implant it into whatever crop they desired, in this case, an eggplant. Implanting the gene would allow the eggplant to produce the toxins on its own, effectively producing its own pesticide. The toxin in B. thuringiensis works by being ingested in crystal form where the crystals separate and bind to proteins on the gut cells and cause them to burst. Propelled by the movement of its hemolymph, the insects gut juices are pushed into its body cavity where it is left to succumb to infection, paralysis, and death. In the case of the eggplant, Bt eggplants would kill only the fruit and shoot borer and possibly closely related species, leaving other insects and creatures unharmed. Bt was a popular spray choice for organic farmers because "In addition to their selective lethality, the bacterial toxins degraded in sunlight and washed away in rain, rather than contaminating wild habitat and sources of drinking water." meaning that this pesticide had few side effects per say to the environment. The only catch to this pesticide is that it needed to be applied very frequently, often every three to four days.

This is where the scientists come in. If the scientists effectively implant the toxin making gene from the bacterium into the crops than the crops will no longer need to be sprayed. The crops will create their own toxin which has been tested to be selectively lethal, making it relatively harmless to humans and would save farmers loads of money on fuel because the plants would no longer need to be sprayed. Scientists mention using agrobacterium tumefaciens to implant the B. thuringiensis gene into the crops, as the agrobacterium evolved to inject material into plants in order to aid infection. With genetically modified plants such as these, farmers could see a rapid increase in profits because they would be generating a stronger crop yield and they would save on costs for transporting and spraying the pesticides.

Article:       http://www.scientificamerican.com/article.cfm?id=farming-a-toxin

Sub-Article:     http://onlinelibrary.wiley.com/doi/10.1046/j.1365-313X.2002.01401.x/full

Combating Blight in the American Chestnut.

According to an article published at sciencedaily.com there may be a method to combat Chestnut blight in the future. The American chestnut tree is threatened to become extinct. This is occurring because of a fungus know as chestnut blight. Chestnut blight attacks the roots of a tree and produces Oxalic acid that destroys the cambium where the tree grows from so the tree dies. Drs. William Powell and Charles Maynard of the SUNY Collage of Environmental Science and Forestry (ESF) believe they may have a way to save the American chestnut. Powell and Maynard created transgenic American chestnut trees with a gene derived from wheat. This gene in previous tests showed the ability to increase the resistance of poplar trees to fungal pathogens. This is one of many genes to be tested at a site in The New York Botanical Garden. This site is relevant because it is in the area where the chestnut blight was discovered in the United States over 100 years ago. Saving the American chestnut would be a good first step to stopping evasive species from taking over the ecosystems where they don’t belong. Also the economic incentives for food and higher quality lumber could keep money in the American economy. It sounds minor but this research could have direct effects on many people.