The Human Genome Project (HGP) and drug development

HGP summary

Began in 1990 and lasted 13 years Involves identifying all the genes found in

human DNA The human genome has 3 billion pairs of

bases. The particular order of bases is extremely important in determining all of life's diversity

Info stored in databases Database used to identify genes (and so

proteins) involved in disease

Drug development

Info used to create new drugs targeting the identified proteins

Highlighted common genetic variation between people

Some variations make some drugs less effective (asthma drugs less effective for people with a particular mutation)

Companies can use this knowledge to design new drugs effective in people with these variations

Cancer

Example of gene targeted drug development An effective treatment needs to selectively attack mutated cells but leave healthy

cells alone HGP helps involved genes be identified. Allows the possibility of identifying

substances that will interfere with gene expression there Can be done by: terminating gene expression into mRNA (or translation into a

protein). Or killing the mutant cell For colon cancer, cells contain a mutant form of the gene known as K-Ras Healthy cell: K-Ras gene in transcribed into mRNA, the code of which is translated

into a protein regulating and instructing the cell growth, division and maturation Mutated form- gene has the potential to switch normal growth into uncontrollable

growth Search for new drugs that will target the mutated K-Ras gene, research teams use

paired cell colonies (cell lines) that differ in only a single mutated gene (the K-Ras gene)

Using the cell colonies, thousands of drug compounds have been screened. 4 compounds identified that distinguish mutant cells from normal healthy cells

One inhibits the growth of tumours in mice and investigation is ongoing

https://www.youtube.com/watch?v=v_lSXiXb6-o

Bioinformatics

Involves developing methods and software tools for understanding biological data.

Combines computer science, statistics maths and engineering to study and process biological data.

Common uses of bioinformatics include the identification of candidate genes and nucleotides (SNPs) single-nucleotide polymorphisms 

Often, such identification is made with the aim of better understanding the genetic basis of disease, unique adaptations, desirable properties (esp. in agricultural species), or differences between populations.

Pharmacogenomics

The study of the role of genetics in drug response. It deals with the influence genetic variation on drug response

in patients by correlating gene expression or SNPs with drug absorption, distribution, metabolism and elimination, as well as drug receptor target effects

Aims to develop drug therapy, with respect to the patient’s genotype, to ensure maximum efficacy with minimal adverse effects 

Hoped that drug treatments can deviate from what is dubbed as the “one-dose-fits-all” approach.

It attempts to eliminate the trial-and-error method of prescribing, allowing physicians to take into consideration their patient’s genes, the functionality of these genes, and how this may affect the patient’s treatment

Ethical Issues

The ethical issues raised by the human genome project can be grouped into two general categories:

Genetic engineering, and Genetic information.

Genetic engineering

Addresses issues concerned with genetic manipulation or what is sometimes called “genetic engineering”.

Possibility of genetic interventionThe distinction between somatic cell and

germ line intervention and,The distinction between therapeutic and

enhancement engineering.

Distinction between somatic cell and germ line intervention

Somatic cell manipulation alters body cells, which means that resulting changes are limited to an individual.

Germ line manipulation alters reproductive cells, which means that any changes will be passed onto future generations.

The use of somatic cell interventions is regarded as ethically acceptable

Whereas germ line interventions have more significant ethical concerns.

The distinction between therapeutic and enhancement engineering.

Therapeutic engineering occurs when genetic interventions are used to rectify diseases or deficiencies.

Enhancement engineering attempts to extend traits or capacities beyond their normal levels. E.g increasing height.

Enhancement engineering is widely regarded as being ethically problematic.

Unforeseen Consequences

Question of future generations agreeing with their predecessors views about the desirability of the traits.

May feel limited by choices we have made regarding their physical, cognitive, or emotional traits.

Genetic Information

Consists of ethical questions pertaining to the acquisition and use of genetic information

What parameters should be set for the acquisition and use of genetic information?

Abuse of information

Fear that employers and health insurance companies would refuse to hire or refuse to provide health insurance

If it is considered fair and proper to identify applicants with high cholesterol and/or a family history of heart disease, and to charge those applicants higher premiums, why should it be considered unfair to utilize genetic testing in the future to accomplish the same goals?

Potential for conflict between a parent’s choice and a child’s welfare.

What if a parent refuses to consent to a test that is clearly in their child’s best interest?

What if a parent decides to pursue a genetic “enhancement” that involves significant risks for a child, or that may limit a child’s life prospects?

Moral Issues

Increased abortion rates.  Loss of identity because “cloning threatens

confusion of identity and individuality, even in small-scale cloning.”

We would be transforming procreation into manufacturing; humans “will be products of human will and design,” not products of two adults.

Social implications

Doctors will have to change the way they practice medicine because they will have to treat preventative illnesses.

As a result of this change, doctors may be more at risk for malpractice; specifically, they may be sued for giving faulty genetic advice or failing to provide proper information about known genetic diseases.  

A couple has a child with kidney disease.  The child dies five hours after birth.  Following the autopsy, the parents are reassured that their risks are not increased for having a similarly affected child in a future pregnancy. Litigation begins after their second child was born with the same disorder and later succumbed at 2 years of age.  Their physician had failed to recognize that this particular kidney disorder was inherited as an autosomal recessive condition and that their risk in each subsequent pregnancy was 25%.

Physicians will have to become knowledgeable enough about genetics to decide when to refer a patient to a medical geneticist.  

In order to gain such knowledge doctors may have to go back to school and learn more about preventative medicine; consequently, doctors will have to put their practice on hold.  

This will have a profoundly negative effect on doctors because there will be too much information to remember, and many may not be able to put their practice on hold for several years while going to school.