Cracking the Code of Life

It was Monday, June 26, of the new millennium. We were gathered in the McMillian auditorium at Baylor College of Medicine in Houston, Texas. The majority of us were from the school’s human genome sequencing center, one of the four centers in the U.S. assigned to sequence the human genome. The event was a teleconference from Washington announcing the completion of the draft sequence of the human genome. The immense euphoria in the air was vindication enough of my decision to pursue a graduate degree in human genetics. It was an important event in my life because of my fascination for one of humanity’s greatest scientific ventures to decipher the so-called book of life. In an attempt to demystify this monumental achievement, often hailed as being more significant then stepping on the moon, I decided to write about what it means to me and what it could possibly mean to you. This is not an attempt to trivialize the science involved, nor the implications (positive or negative), but really a desire to put in as simple terms as possible an achievement that the human race can be proud of.

In order to understand the need for such a daunting project, one needs to know something about the human genome and its composition. The human genome is the genetic blueprint of the human being, containing all information possible for how cells reproduce and carry out functions vital to life. It is a code written in 4 letters: A, T, C and G, standing for the building blocks of the molecule of life called DNA. All the information is encoded into a string of approximately 3 billion of these letters. Think of DNA like any other text: for instance, while the English text is written in 26 letters, DNA is written in only 4. Within these letters of DNA there are between 50,000-100,000 interesting ‘paragraphs’ which are the genes. Even though they constitute only 3% of the book, genes are of real significance because the instructions that they contain in the A, T, C and G language actually spell out the proteins in our body. Proteins are crucial for the proper functioning of almost all activities needed for life. Hence, DNA can be thought of as an archive in which the instructions for making proteins have been written down. The genome is divided into 46 chromosomes that are matched into 23 pairs, one obtained from the father and the other from the mother. The sequence of the genome is the order in which the letters run down the strands of DNA. In order to determine the sequence of the complete human genome, powerful computers were used along with sequencing machines to read through the 3 billion letters of DNA.

The race to sequence the complete human genome pitted an international, publicly-funded consortium (the human genome project-HGP) against a private firm called Celera Genomics. Celera claims to have completed 97% of the genome, while the HGP is further behind. Loose ends like gaps and errors within the sequence will be cleared up over the next two years, but even then the book of life will be unreadable because it is written in a foreign language, hence making its interpretation complex. The interpretation phase is not a trivial task since researchers need to search the whole sequence with a fine tooth comb to get to the genes. Even then, knowing the genetic code does not automatically translate into knowing what protein is produced where in the body, what it does, and how it interacts with other proteins. These details are vital for knowing how the genetic code actually translates into a fully functional human being. However, the laying down of the genetic code was a necessary prerequisite to answering these questions. The sequence is just a starting point to help us understand the molecular basis of disease, something we have been unaware of for the majority of illnesses that plague us.

So now that we have the draft sequence, what next? Having deciphered the code and making it available on the Internet gives researchers a head start in their search for disease genes. Conditions such as diabetes, schizophrenia and heart disease that were known to have genetic risk factors difficult to nail down will enjoy an acceleration in discovery of their genetic triggers, thanks to the set of power tools that the genome project has unleashed upon the scientific world. The database opens the door to the possibility of tailor-made treatments based on an individual’s unique genetic makeup, and furthermore, knowing the genes can tell us about novel targets for developing drugs. The use of gene therapy to cure or even eliminate devastating inherited disorders may be just around the corner. We can really look forward to a markedly transformed concept of what a disease really is: a precise definition may be gleaned making diagnosis more accurate and therapy extremely focused and swift.

Having knowledge of our biological essence has its dark side, just like scientific achievements in general. With the advent of this type of technology we need to gear ourselves for a world that is obsessed with designer lifestyles: so why not ‘designer babies’, set to please our egos? Genetic discrimination is something that cannot be taken lightly any more. We need stronger laws to protect privacy; laws against genetic discrimination and insurance issues need to be dealt with. One can imagine various ways to misuse this information, but this information is so fundamentally important to us collectively as a race that if we are not freely able to utilize it for the benefit of society then we all stand to loose. Patenting the genome as practiced by the private sector has stirred the debate whether anyone can really lay claim to it. If this happens then only a select few of the strongest biotechnology firms will be able to use it for monetary gains. Even researchers at large will be unable to access the valuable information that the genes hold. Hence, it is essential that our genetic heritage be made equally accessible to everyone. With all the hype in the wake of this breakthrough, it is important that we are not left with the impression that we are merely products of our genomes. It is really the interaction of our genomes with the environment that has a major impact on our lives and health.

A look at the genome of any two people indicates sequence identity of up to 99.9%, and this goes to show that our similarities really outweigh our differences. Maybe some day this will be a motivating force for people to unite as a race rather than highlighting their ethnic differences. Part of the effort to decipher the human genome was an attempt to map and sequence the genomes of some ‘model’ organisms, including bacteria, yeast, worms, flies and mice. Comparing the genome sequences of all these organisms to that of the human indicate the fascinating manner in which nature has conserved the basic thread of life. This will hopefully help us respect other life forms as fellow passengers on this earth, and not merely present for us to exploit ruthlessly.

We are ready to initiate the intricate process of interpreting our genetic code so that it benefits us rather than blowing up in our faces. Before that, however, a lot of thought and discussion is required to ensure that we are really at the beginning of what may turn out to be a fascinating era for humanity.