WHAT IS THE IMPACT OF THE HUMAN GENOME PROJECT FOR DRUG DEVELOPMENT? Arman & Fin

What is the Human Genome Project?  The genome is the collective name for all the genes in the set of chromosomes of an individual, including positions and sequences of genes on the chromosomes as well as the base sequences within the genes  The Human Genome Project (HGP) began in 1986 and initial analysis of the entire set of human genetic instructions was published in February 2001

Main aims of the HGP: To:  Identify all the genes in human DNA  Map the positions of the genes on all the human chromosomes.  Determine the sequences of the chemical base pairs that make up human DNA  Develop suitable technological tools for analysis and subsequent use of the genome  Store the DNA information in suitable databases for easy retrieval and analysis  Make the technological and genome information available to all interested parties, including biotechnologists, industrialists, pharmacists and the medical profession  Address the ethical, legal and social issues that may arise from the project

Outcomes of the HGP  It was initially though that it would take upwards of 20 years to decipher the full human genome but due to developments in bioinformatics, progress was more rapid  In 2001 a working draft of the human genome was published – work continues with some sections 99.99% accurate  Sequence is immediately published online, making it a freely available resource to scientists around the world

Discoveries  The human genome is now thought to be around bases long and to contain to genes  An average human gene is around 3000 bases in length but great levels of variation occur  Function of most genes still unknown  Around 1.4 million locations where SNPs have been located  Non-coding sequences make up at least 50% of the human genome.

Identification of new genes  Many disease genes have been identified, including the breast cancer gene BCRA2 and the total colour blindness genes GNGA3 and GNGB3. Several genes associated with Parkinson’s disease have also been identified including DJ1 and PINK1.  Now possible for a candidate gene that may cause a particular disease to be located and then screened for mutations in affected individuals.  Through this method six genes have been identified to increase susceptibility to Alzheimer’s disease.

Identification of new drug targets  Drug target is a specific molecule with which a drug interacts  Before the draft human DNA sequence was published there were only 500 drug targets  Scientists have already discovered thousands of new and potential drug targets.  In 2008 a study identified 80 genes which influence the formation of the protein alpha-synuclein, which accumulates in the brains of Parkinson’s disease patients. Investigating the genes may lead to new drug targets to develop a cure for the disease.

Preventative medicine & improved drug development  Pharmacogenomics is the study of how genes affect a person's response to drugs.  In some people a drug works well with few side affects, in others the same drug is ineffective and has major side affects  This may be due to differences in the individual’s genome, depending on which of the 1.4 million SNPs a person possesses. Drug prescription is based on a recorded system of trial and error.  It is hoped that information about a person’s genome will enable doctors to prescribe the right drug at the correct dose.  If people knew about their mutations associated with a particular disease, they may be able to make lifestyle changes or opt for preventative treatment in order to reduce their risk of disease.

Social, moral and ethical issues with this technology:  Access to information regarding an individuals genome and how it should be used.  Confidentiality of your genetic information – not distributed without permission.  Genetic discrimination – societies views on genetic information may change and lead to social deprivation of people with genetic imperfections or cause them to be stigmatised.  Foetal genetic testing – must make potential parents aware of the accuracy and reliability of the tests and before individuals give consent for procedures they must be adequately informed about complex and controversial procedures, and how to assess genetic information for reproductive decisions and about the reproductive rights of parents and children.

Social, Moral and ethical issues with this technology:  Genetic tests must be reliable and interpretable by medical professionals who must be trained on implications and capabilities of genetic information.  Should tests be carried out for adult onset diseases/ diseases with no treatments? – Arguably not the parents choice/could cause unnecessary stress, also tests may not reliable.  Genes causing disease – are they acceptable for genetic diversity?– is misbehaviour due to genes/ is it able to be controlled? – are they necessary?  Publicizing of genomes – may lead to commercialisation of products, rights and patents – who is trusted with this data?

Do the issues underpin/undermine research work?  Creating drugs for specific variations – increase research costs and increase costs of drugs – may lead to a two tier health system where only the wealthier can afford treatments.  Revealing no treatment for certain variations – could be psychologically damaging for some as they would have no hope. These issues seem to partly undermine research work as the complications involved with genomes and access to the information coupled with the expense of drug developments for numerous variations. The lack of certainty in these tests also seems to be more damaging than useful.