What is Genetic Engineering?

By: The FHE Team

This is a good article for the uninitiated or anyone that wants a very broad, fundamental overview of the subject of genetic engineering.  All of the topics covered in this article are dealt with more in-depth throughout the rest of this Genetic Engineering Section of the Future Human Evolution website.

Inside This Article

  • We’re going to tackle some of the more troublesome genetic terminology for you right up front, provide you a DNA visual model of them so you can see how all the key genetic “parts” fit together within a cell, then in the length of one paragraph tell you what it’s all about; “genetic engineering in a nutshell”.
  • After that we dive right into the ways genetic engineering can be applied to humans for everything from treating the diseases of today (gene therapy) to eliminating genetic diseases from tomorrow’s gene pool (germline engineering).
  • Lastly, we will give you a glimpse on where science and technology stands today on Designer Babies.

The Definition of a “Gene”

And other important (but confusing) terminology

Since Gregor Mendel’s experiment on the study of inheritance patterns of peas in 1857, the theory of “genes” controlling our physical being came into light. This evidence gave firm affirmation that the as yet undefined gene carries hereditary information from generation to generation, in other words genes are responsible for genotypic (molecular DNA type) and phenotypic (physical type) characteristics of individuals. Four decades later in 1902, Walter Sutton and Theodar Boveri proposed that “chromosomes,” supersets of DNA, are responsible for carrying genetic information. In 1953, James D. Watson and Francis H. C. Crick put forth a model for the physical and “double helix”-shaped chemical structure of DNA molecules that serve as the backbone of DNA; series of four-lettered, chemical base-pair combinations called nucleotides, and specific segments of nucleotides that give rise to potential traits called genes.

That’s a whole lot of terminology for one paragraph, so let this picture help you out:

chromosomes-genes-nucleotides-dna-base-pairs-and-the-future-of-human-evolution

Genetic Engineering in a Nutshell

With all this known genetic information researchers realized it was possible to develop technology for the rapid addition, change, or deletion of specific genes which then quite simply and naturally led to the development of genetic engineering as a science and technology. Genetic engineering mainly requires a gene to be transferred into a host cell, using a vector- biomaterial that facilitates merging of the new DNA with that of the host cell’s DNA. The whole process is called transformation. A good term to remember is “recombinant DNA”.  That’s what a human-edited strand of DNA is called- it has been taken apart and the “recombined” to make a better organism.

From a practical application perspective in everything from crops, livestock, and bio-based consumer goods (e.g. cotton), Genetic Engineering comes in two basic varieties: “Intra-species” (within a single species), and “Interspecies” (between two or more species):

  1. Intra-species improvement: Within a single species, creating recombinant DNA to produce literally next generation results that might normally take decades or even centuries of traditional plant and animal breeding to achieve
  2. Interspecies improvement: It can be used to move genes and the genetic characteristics of one type of organism’s cells to another type to produce beneficial results.  Genetic engineering makes it possible to shuffle information between entirely unrelated species (e. g. transferring Bacillus thuringiensis cry toxin gene as an effective pesticide in cotton to protect it from pests).

Genetic engineering also shows tremendous potential for improving the health and well-being of humans.

Human Genetic Engineering

In humans, as with any other organism, genetic engineering is simply the editing of genes in living cells. Genes, as alluded to before, are merely segments of DNA (nucleotides) that are responsible for traits in the physical body (phenotype). This includes all heritable characteristics including coloration, height, certain intelligence factors, etc., as well as the predisposition or immunity to particular diseases and genetic defects.

Not all human genetic engineering is targeted at improving future generations (aka germline engineering)- in fact human genetic engineering today for all intents and purposes is limited to Gene Therapy: correcting genetically defective cells in a single living human.

Gene Therapy vs. Germline Engineering

With regard to reproductive classification, there are two types of cells in the body:

  1. Germ cells aka “Gamete” cells – Often used interchangeably with “gamete”, germ cells are those capable of turning into gametes, i.e. sperm and egg cells which combine to form the next generation of human.  Genetic characteristics contained in these cells are “germline” as they will be passed on from one generation to the next (down the germ-cell line).
  2. Somatic cells – These are basically every other type of cell in the body (some 200 varieties) except the germ cells.  Somatic cells can undergo any amount of change without any effect on offspring.  Gene therapy usually targets these non-reproductive, somatic cells (because that’s where most diseases occur).

Human Gene Therapy

Nearly every disease has a genetic component.  Either the gene is missing in part or in whole, or its base pairs are out of normal sequence or otherwise damaged.  Gene therapy targets not only the specific cells that contain the DNA, but the specific strand of DNA that is defective.

Genetic Disorders

Both environmental and genetic factors have roles in the development of any disease. A genetic disorder is a disease caused by abnormalities in an individual’s genetic material (genome). There are two classifications of disorders that occur at the gene level: (1) single-gene, and (2) multifactorial (involving multiple genes).  Chromosomal and mitochondrial defects also lead to “genetic” diseases but do not occur at the gene level and are covered elsewhere on this site.

(1) Single-gene (also called Mendelian or monogenic) diseases – This type is caused by changes or mutations that occur in the DNA sequence of one gene. There are more than 6,000 known single-gene disorders, which occur in about 1 out of every 200 births. Examples are Huntington’s disease, sickle cell anemia, cystic fibrosis, and Marfan syndrome. Single-gene disorders are inherited in more easily-identifiable patterns than are their more complex alternative, multifactorial disorders.

(2) Multifactorial (also called complex or polygenic) disorders – This type is caused by a combination of environmental factors and mutations in multiple genes. For example, breast cancer is now known to be influenced by genes found on seven different chromosomes. This “matrixed” or interactive nature makes it much more difficult to analyze than a single gene or chromosomal disorder. Many of the most common chronic disorders are multifactorial and include Alzheimer’s, heart disease, obesity, high blood pressure, diabetes, cancer, and arthritis.

As a note for later in this article, multifactorial inheritance is also associated with heritable traits such as height, eye color, and skin color.

Gene Therapy Treatments and Methods

In order for gene therapy to be successful, “good genes” or “Therapeutic DNA” must replace dysfunctional DNA in most of the affected cells. Obviously a technician is not going to take a needle and inject every individual nucleus in the diseased area of a person’s body (thousands or even millions of cells).  Scientists looked to nature to find a solution; a vehicle that already performs a similar function. In one of the greatest turn-abouts in natural history, rather than the harmful virus hi-jacking and invading healthy cells and turning them into destructive viral making machines, we humans have managed to hijack the virus’ own self-replicating mechanism replacing it with a healthy version of our target DNA for the purpose of turning it loose to “infect” our unhealthy cells with the new, improved, healthy DNA.

Back to terminology, this re-purposed virus is called a “vector”. Vector as concept, term, and tool is important in the context of both gene therapy and genetic engineering. In traditional medicine, a vector is an organism that does not cause disease itself but which spreads pathogens from one organism to another. For example a mosquito, considered a vector, can carry heart worm or malaria from one host to another without suffering from the condition itself.

Geneticists have borrowed the concept for the transmission of genes.  In genetics, a vector is simply a molecule containing, and used to move, external healthy DNA into targeted dysfunctional host cells.  As described above, vectors usually contain a virus to help assimilate the healthy DNA onto the dysfunctional DNA strand in the host cell but there are other means of getting our therapeutic DNA into damaged nuclei.

  • Vectors, of which there are many varieties, may employ a similar technique but using bacteria as the facilitator.
  • They may also have a fat or “lipid” coating similar to the fat or lipid coating of the target cell to help the vector bond to the target cell and naturally absorb/pass the DNA from the vector to the nucleus of target cell.
  • Genes can also gain entrance into cells when an electrical charge is applied to the cell to create tiny openings in the membrane that surrounds a cell in a technique that is called electroporation. Not very useful on a large scale as you might imagine.
  • Therapeutic DNA also can get inside target cells by chemically linking the DNA to a molecule that will bind to special cell receptors. Once bound to these receptors, the therapeutic DNA constructs are engulfed by the cell membrane and passed into the interior of the target cell. This delivery system tends to be less effective than other options.
  • Researchers also are experimenting with introducing an artificial “47th” human chromosome into target cells. This added chromosome would reside next to nature’s 46 without affecting their functions and with causing mutations. Scientists believe that the body’s immune system would accept it more readily than typical therapeutic insertions due to its naturalistic construction and autonomy. Scientists have already successfully inserted such a human chromosome into mice as proof of concept. The mice are fine.

There are numerous gene therapy clinical trials on-going throughout the world. In fact a recent study (Feb 2013) identified nearly 2000 completed, ongoing, or approved gene therapy trials for the period 1989 through the 2013 date of publication. At the present time, in the United States the Federal Drug Administration has not approved any gene therapy treatments for commercial distribution or availability.

The website www.HumanBiotechnology.org , amongst the many aspects of human biotechnology they cover, will be monitoring the potential for this lack of commercial gene therapy approval to change and will be following the organizations and trials most likely to succeed.

Human Germline Genetic Engineering

Human germline genetic engineering refers to the intentional altering of DNA in germ cells that will lead to the change being a natural part of the reproductive cycle, passing the improved DNA from one generation to the next.

The techniques used in germline engineering are much the same as those used in gene therapy except that healthy gene insertion into a target cell can be done using a wider variety of methods.  This is because instead of needing to treat say large amounts of a diseased liver (potentially tens of thousands of somatic cells) as in gene therapy, germline engineering need only target either the gamete cells (egg and/or sperm) or an early embryonic cell: a “zygote”, the originating single cell from a sperm-egg union, or a “cytoblast”, the first few cells divided from the zygote.  Changes made at these early stages will then multiply as the organism matures with the therapeutic gene replicated naturally in every cell.

As a result of fewer cells being targeted, the injection method referenced in the gene therapy section as impractical now makes sense. It is called Microinjection.  Similarly, a less-than-cell-sized metal sliver can be coated with therapeutic DNA and gently and precisely “shot” into a target cell using the world’s tiniest shotgun in a process called “Bioballistics.” Whoever said scientists don’t have a sense of humor?

The key difference then, between gene therapy and germline engineering is heritability: The latter offering the ability to permanently eliminate all genetic disease (including Cancer) and many aging ailments not only improving the quality of human life but living, and contributing, and enjoying life longer.

An important note to those who would confuse heritability with obligatory permanence. Germline engineering allows for the possibility of permanence. What it is in reality is the ultimate in flexibility. At any point in the future, whether it be the next generation after an alteration (reference the accelerated definition of generation), 10 generations down the road, or a thousand, genetic changes may be modified back to their original configuration, or further tweaked to achieve the desired result.

Designer Babies: The State of the Art

We have other articles on the site dealing specifically with Designer Babies and the future of human evolution. This section of this article will simply give you the brief, bare facts.

  • There are genetic processes in place to prevent a child from permanently having/carrying/passing on over 400 genetic diseases.
  • Such genetic processes are not engineering: no one is manipulating DNA. Rather they are selecting a disease-free embryo from among several created by the parent’s gametes.
  • This selection process is called “Preimplantation Genetic Diagnosis” and is commercially available.
  • The only trait parents may currently choose via preimplanation genetic diagnosis is gender.
  • Gender is relatively easy to detect through a microscope and an embryo with the parent-preferred gender is selected from among several created by the parents’ gametes, for implantation into the mother.
  • Science and technology is not at the level to “engineer” parent-preferred traits (i.e. manipulate genes directly).
  • Difficulties to overcome revolve primarily around reliably identifying what genes, or more importantly what combination of genes, result in what traits and have what as yet undetected subtle effects on other traits.  This is the Multifactorial (also called complex or polygenic) gene complication referenced earlier in the article.
  • Another difficulty is the technical prowess of current methodologies: getting the therapeutic gene in the exact or at least an effective location along the target cell’s six-foot long strand of DNA.

Daily progress is being made by scientists and technicians from around the world toward overcoming the practical challenges in allowing parents the freedom to choose a happier, healthier legacy for themselves and their children.

Society’s concern should not be how to prevent such progress, rather how to make it available to all that wish to take advantage of its humanitarian benefits.

References

  1. Pensak, M. J.; Lieberman, J. R., Gene Therapy for Bone Regeneration. Current pharmaceutical design 2013.
  2. Hirschler, B., Doctors test gene therapy to treat blindness. Reuters O5/01/2007, 2007.
  3. How Viruses Work by Craig Freudenrich, Ph.D. http://science.howstuffworks.com/life/cellular-microscopic/virus-human.htm
  4. Human Genome Project Information: Gene Therapy http://web.ornl.gov/sci/techresources/Human_Genome/medicine/assist.shtml
  5. Human Genome Project Information: Genetic Disease Information http://web.ornl.gov/sci/techresources/Human_Genome/medicine/assist.shtml
  6. Gene therapy clinical trials worldwide to 2012–an update, The Journal of Gene Medicine Volume 15, Issue 2, Article first published online: 27 FEB 2013
  7. Barbara E. Stranger and Eli A. Stahl: Progress and Promise of Genome-Wide Association Studies for Human Complex Trait Genetics, Genetics February 2011 vol. 187 no. 2 367-383
  8. The Independent: http://www.independent.co.uk/news/science/exclusive-mice-with-human-chromosomes–the-genetic-breakthrough-that-could-revolutionise-medicine-8701357.html , 11 July 2013