Figure 1. Photo of the original model developed by Watson and Crick after studying Rosalind Franklin’s x-ray diffraction data. At their Nobel acceptance speech they both credited Ernst Schrodinger with the basic discovery of DNA in his book What is life.
Genetic engineering started more than 15,000 years ago when humans first domesticated animals and plants. Modern genetic engineering may be defined as the direct transfer of DNA from one organism to another. Our understanding of DNA and Genes is a story that built over many centuries step by step.
Gregor Mendel’s 1865 study of inherited traits in peas was one giant step forward. Mendel was a monk who had studied physics but turned to agricultural products, discovering rules that govern variety through deliberate breeding. Another giant step was theoretical prediction of a single complex heredity molecule in the nucleus of every cell made by Ernst Schrodinger, a Nobel Laurate in Physics, who shared the Nobel Prize for Quantum Mechanics with Paul Dirac (my former PhD committee member and close friend). A third leap forward was determination of the structure of DNA by Watson and Crick in 1953 after they had studied Rosalind Franklin’s x-ray results.
The beginning of modern genetic engineering was the direct transfer of DNA from one species to another. This was first done in 1972 by Stanley Cohen and Herbert Boyer. Rudolf Jaenisch gave us the first genetically-modified animal using this technique in 1974. Two years later, the genetic engineering technology was commercialized, with a genetically-engineered bacteria that produced somatostatin, a new drug, which was followed by insulin in 1978. The next big breakthrough came in agriculture in 1983, when an antibiotic-resistant gene was inserted into tobacco, creating the world’s first genetically-engineered plant. Many agricultural advances followed that allowed scientists to manipulate and add genes to a variety of different plants and other organisms.
In 1992, China leaped forward with the first commercialized genetically-engineered plant using a virus-resistant tobacco plant. In 1994, the first genetically-engineered food was marketed. It was called the Flavr Savr tomato. In 2000, a paper published in Science discussed golden rice, the first food engineered with increased nutrient value. Twenty-nine countries had commercialized at least one genetically-engineered biotech product by 2010. Modern genetic engineering may be defined as the manipulation of an organism’s genes using biotechnology. There are many techniques. We have the potential to reprogram the aging software stored in our DNA. This is exciting to me and other scientists. Science tells us that with much research, we can control aging by reprogramming our own cells, which is also called genetic engineering.
Figure 2. Genetic engineers working to improve life. Credit Wikipedia
Modern genetic engineering differs from the older methods of breeding by selection. Gene splicing and recombinant DNA technologies are also known as genetic modification (GM). These terms apply to the direct manipulation of an organism’s genes. Traditional breeding is an indirect method of genetic manipulation.
In 1980, Martin Cline modified a human genome; however, the first successful nuclear gene transfer in humans, approved by the National Institute of Health (NIH), was conducted in 1989. Up until recently, over 2300 clinical trials have been conducted and many more will follow shortly.
Modern genetic engineering utilizes new tools such as molecular cloning and transformation to directly alter the structure and characteristics of target genes. Genetic engineering techniques have been proven to be successful in many products and in numerous other applications. Some examples include the improvement of crop technology and in the manufacture of synthetic human insulin through genetically-engineered bacteria. It is said the first gene therapy successes in the year 2000 related to agriculture. However, human success was also dynamic and related to human aging:
1) April 2000, France. Five children with Severe Combined Immune Deficiency (SCID) were successfully treated with gene therapy.
2) August 2000, Tufts University, Boston, USA. Jeffrey Isner rang in the new century announcing successful treatment of heart muscle blood supply using vascular endothelial growth factor gene.
Figure 3. Maria A. Blasco and Bruno M. Bernardes de Jesús (co-authors) in the CNIO lab in Madrid, Spain, one of the first laboratories to use genetic engineering to increase lifespan. They uncovered the bais for CRIPR technology. Credit: CNIO
As early as 2007, these researchers started work on genetic engineering to increase lifespan. On May 14, 2012, scientists studying aging at the Spanish National Cancer Research Centre (CNIO), including director María Blasco and colleagues, reported that mouse lifespan could be extended up to 24 percent. These results were from a single treatment acting directly on the animal’s genes using gene therapy. The authors claimed this was a new strategy employed for the first time to combat aging. The therapy was determined to be safe for mice, but more testing would be required before human trials.
The work was published in the journal EMBO Molecular Medicine. The CNIO team, in collaboration with Eduard Ayuso and Fátima Bosch of the Centre of Animal Biotechnology and Gene Therapy at the Universitat Autònoma de Barcelona, study the impacts on one-year-old adult and two-year-old adult mice using a type of gene therapy. The scientists reported a “rejuvenating” effect in both cases.
Promising life extension technologies are being investigated with potential for preventing many diseases, extending human life by decades and centuries, and most importantly restoring youthful function to people aging until the end. Anti-aging gene therapy is defined as the reprogramming or delivery of genes to treat or prevent disease and/or increase healthy lifespans.
One aspect of genetic engineering will introduce genetic material into cells to compensate for abnormal proper proteins. In addition, the function of the gene may be reprogrammed to prevent disease and/or cell death. This technology uses a carrier called a vector to genetically engineer the gene. The vector may be injected “directly into a specific tissue in the body,” Maria Blasco explained. There it can be adsorbed by individual cells over time if conditions are favorable for this event. For example, assume a defective gene causes an important protein to be missing or defective. Then genetic enginneering may introduce a normal copy of the gene to rejuvenate the process.
One of the biggest discoveries in the field of gene therapy is attributed to the Japanese researcher Shinya Yamanaka.
Figure 4. Japanese scientist Dr. Shinya Yamanaka who is a key player in genetics research. Credit Google
Dr. Yamanaka was awarded the Nobel Prize in 2012. He identified four genes, which are now referred to as the “Yamanaka factors.” When triggered, these factors can convert any adult cell into induced pluripotent stem cells (iPSCs). The method is now referred to as cellular reprogramming. The iPSCs can divide indefinitely and become any cell type. That means they behave like embryonic stem cells. In San Diego, scientists at the Salk Institute were able to turn back “the cellular clock” by triggering, through gene therapy. This work used the Yamanaka factors to reprogram cells in 2016. The researchers at Salk Institute further reported that applying this cellular reprogramming for brief periods of time not only rejuvenated human cells in a petri dish, it more importantly reversed the effects of aging in live mice from a genetic rapid aging disease known as progeria.
This rare genetic disease causes human children to age rapidly as well as mice. These researchers regenerated damaged tissues and organs in the progeria-diseased animals and extended their lifespan by 30%.
The bad news is that activating the Yamanaka factors can cause cancer if applied continually. The San Diego-based Salt team needed to limit the application to two days a week to prevent cancer in the diseased mice. The team is positive about starting human trials.
Figure 5. Is this amazing anti-aging science aa fad or will it become the largest business in the world in 20 years?
Dr. Mark Kingston Levin award-winng author of 30th Century: Escape.
For questions and comment contact the author by email at firstname.lastname@example.org
Dr. Levin was born and grew up in Vermont with many winters spent in Florida as a child. As a teenager he wrote poetry, served as a lifeguard and played football. He currently enjoys sailing, exploring underwater caves, snorkeling, writing science fiction and other pursuits. After working on the Apollo and Mars projects, he returned to school to study under Nobel Laureate Paul Dirac, obtaining his PhD in 2.5 years. Dr. Levin founded two companies and served the science policy apparatus in President Ford’s administration. He has been published over 44 times in scientific literature and was awarded over 32 US patents. The science fiction writer is now emerging with his first work, a trilogy entitled 30th Century. The first award-winning book, 30th Century: Escape, is currently available on Amazon. Book two in the series, 30th Century: Revived, was published April 29, 2018 and is on B&N, Amazon and many others.