Eugenics, Euphenics and Gene therapy

Eugenics (Gr. Eugenes = wellborn) is the science of improving quality of human race and obtaining better heritage by judicious breeding.¹It deals with improvement of human race by applying the laws of genetics. Likewise, Euphenics deals with improvisation of human race by control or treatment of genetic diseases of humans. These genetic diseases mostly refer to inborn errors of metabolism in which the missing or defective enzyme has been identified.¹ In today’s era where science has seen new heights as never seen before, the science of genetics has caused another human revolution through the application of genetic engineering. Now, there exists a technique through which genetic defects can actually be corrected, which is referred to as gene therapy.

1. 1 Eugenics

Eugenics is the method which involves improvement of germplasm of existing individual for betterment of human society. According to this concept, it is desirable to reduce genetic load (negative eugenics) and to improve the genetic makeup (positive eugenics) of the human population.²The various proposals on eugenics comes along with a number of religious, social, moral, and political issues.

1.1.1 Positive eugenics

Positive eugenics aims to improve the genotypic constitution of human population so that the individuals become better adapted and fit than their predecessors.²The percentage of desired traits can be increased by encouraging the marriages between individuals possessing ‘desirable’ phenotype (i.e. controlled mating and reproduction). Laws were enacted in the Nazi Germany that banned marriage between members of the ‘superior’ (Aryan) and other races.² Marriage law in Indian caste system seems to be based on similar consideration, as the marriages between members of different castes in not looked upon favorably. However, positive eugenics as previously stated is quite controversial, and unfit under the current sociopolitical environment.

1.1.2 Negative eugenics

Negative eugenics involves measures to eliminate or reduce the frequency of defective genes in human population. These measures represent following two approaches:

Reducing the reproductive success of individual carrying deleterious genes without adversely impacting the quality of their lives
To correct the defective genes of such individuals through genetic surgery²

1.2 Euphenics

The concept of euphenics involves symptomatic treatment of genetic diseases of man. According to Lederberg, Euphenics consists of nutritional and other measures

, including surgery, which permit a normal development, function and more importantly, reproduction by otherwise inferior or deleterious genotypes. Some good examples of euphonic measures are: regular administration of insulin to diabetics, dietary regulation of alkaptonurics, rescue of hemophiliacs through regular blood transfusions, etc.²

Following Euphenics measures can aid in eliminating certain fatal genetic diseases:

Intake of missing enzyme

One of the possible euphenic measure for the future would be to supply the known missing enzyme to individuals that would allow their cells to complete the required biochemical reaction. Many attempt to do this have been made without much success. Immunological difficulties are encountered since the enzymes being supplied are antigenic and the body produces antibodies against them.

Increasing role of genetics to medicine

Through research and extensive studies, it has been found that increasing number of human diseases have a genetic basis. Three per cent of all human have hereditary diseases which are transmitted in a Mendelian fashion. Cancer and heart disease, which account for the deaths of thousands a year, are also known to have some heritable component. The future goal of immunogenetics can be to suggest the ways by which individual having genes for cancer may develop resistance for this disease. Similarly, an understanding of the genetic basis of heart diseases would alert persons from families with an incidence of the disease to the possibility of incurring heart conditions in the future. This might cause them to alter their diets and life habits accordingly resulting on timely intervention.¹

1.2.1 Demerits of Euphenics

The action of restoring affected individuals to normalcy by euphenic measures directly counters the forces of natural selection. Natural selection is foundation for the evolutionary strength of a species. For example, pku (phenylketonuria) homozygote are normally not able to reproduce, hence the harmful mutations are not transmitted to the future generation.¹ However, when the individuals are applied the euphenic measure, they do develop normally and produce offspring. In this case, every individual of the next generation would be a carrier of this mutation, assuming the second parent of each person being normal.² Thus, many scientists, notably Muller, have expressed fears that the Euphenic measures may lead to an increase in the frequency of deleterious alleles in the population.¹ This eventually adds to our genetic load and weakens the human species from the evolutionary point of view.

1.3 Gene therapy

Gene therapy may be defined in general terms as the introduction of a normal functional gene into cells, which contain the defective alleles of the concerned gene. The main objective of conducting a gene therapy is to correct a genetic disorder or an acquired disorder. Application of gene therapy involves the following basis, developments in genetics, molecular biology and biotechnology;¹

Identification of the gene that plays the key role in the development of genetic disorders.
Determination of the role of its product in health and disease.
Isolation and cloning of the gene
Development of an approach for gene therapy

Disorders that are solved using gene therapy are selected on the basis of the following criteria:

The disease should be life threatening
The gene responsible for the disease should have been cloned
A precise regulation of the gene should be required
A suitable gene delivery system must be available.

Fig 1: Gene therapy using a viral vector can be used to treat or cure certain genetic diseases (Source: modification of work by National Institutes of Health, Openstax)

1.3.1 Types of gene therapy

Gene therapy can be classified into two types: i) germline gene therapy and ii) somatic cell gene therapy

Germ line gene therapy

In case of germ line gene therapy, germ cell (i.e. reproductive cells, sperms or eggs, even zygote) are modified by the introduction of functional genes, which are ordinarily integrated into their genomes.¹ The changes that occurs as a result of germ line therapy are heritable and passed on to the later generations. Theoretically, this method would be highly effective in counteracting the genetic disorders. However, germ line gene therapy is not considered in the present, for application in human being as it could lead to unintended consequences for the future generation. There is also the matter of informed consent, because those who are affected by the germ line gene therapy are unborn and unable to choose whether they receive the therapy.

Somatic cell gene therapy

In somatic cell gene therapy, new functional gene is introduced only in somatic cells, especially of those tissues in which expression of the concerned gene is critical for health. Expression of the introduced genes, relieves the symptoms of the disorder, but this effect is not heritable.² For many disorders, somatic cell therapy is the only feasible option. Many clinical trials applying this technique have been launched for the treatment of diseases like cancer and blood disorders. This approach is further divided into two groups on the basis of the end result of the process:

Addition or augmentation therapy
Targeted gene transfer

Addition or augmentation therapy

In this method, normal foreign gene sequences for the defective genes are introduced. A number of copies of the desired gene are introduced into the cell and are made to express at high level. A variety of viral vectors has been used to deliver genes into target / stem cells, eg. Lymphocytes, bone marrow cells, culture in vitro.¹ Once the in vitro gene correction or gene augmentation has been achieved at the cellular level, the modified cells can be implanted into a suitable region either in an organ of the patient or in the embryo.

Targeted gene therapy

In this technique, genes are introduced by any of the traditional gene transfer methods such as calcium phosphate mediated gene transfer, electroporation or micro injection.¹This is followed by site specific mutagenesis. Gene targeting is more advantageous method of gene therapy for the following reasons:

The targeted gene is changed in a precise and specific manner.
The introduced functional gene is flanked by the same DNA sequences, as the replaced endogenous gene.
No other gene of the genome is affected

REFERENCES

Dr. P.S. Verma, Dr. C.K. Agrawal. Cell Biology, Genetics, Molecular Biology, Evolution and Ecology. fourteenth. (Bharatnagar S, Pradhan S, eds.). S.CHAND & COMPANY PVT.LTD.; 2016.
B.D. Singh. Genetics. Second. Kalyani Publishers; 2018.