When the Human Genome Project was completed in 2003, many saw it as the beginning of a new age. This, they claimed, will unlock the mysteries of cancer, provide cures for Parkinson's, and spark a medical revolution. Today, however, many feel let down.
Most people are aware of the Human Genome Project, and of the claims made on its behalf, yet few understand it in depth. This is understandable. The subject is complicated and most of us are preoccupied with bills and deadlines. But though it is understandable, it is also a pity, since the genome project will shape 21st century medicine.
In 1995, scientists began deciphering the human genome. By 2001 the first results were in, and by 2003 the project was complete. This astonished even the experts, many of whom predicted it would take decades.
Living things are built of cells. Bacteria, for example, consists of just one cell, human beings of billions. Coiled up inside both, you find DNA. DNA, (or deoxyribonucleic acid) is a giant molecule that contains the information necessary for a cell to make proteins. The DNA itself is concealed in thread-like structures known as chromosomes, found in pairs in the cell nucleus. Sections of these chromosomes are known as genes, and a complete set of genes is known as a genome.
The first aim was to discover the sequence of bases – A, C, G, and T – in the DNA molecules that form a genome. The DNA double helix is made up of building blocks known as nucleotides. These consist of a sugar called deoxyribose, a phosphate group, and one of the four bases. The nucleotides link up and you have a DNA molecule.
This molecule looks like a ladder twisted into a spiral; the bases are like rungs on that ladder, forming a four letter alphabet. Three of these letters in a row, ATG, for example, is known as a codon. There are 64 codons in total, and a sequence of them makes up a gene.
Second, they hoped to identify which genes are found where. This was no easy task: the genome of just one human cell is a meter long! Unsurprisingly, thousands of scientists were involved. And the effort was truly multinational, involving 16 different institutions in six different countries. Maps of the chromosomes were made and the location of specific genes pinpointed. These maps then enabled scientists to match a sequence of bases to a particular gene.
When the genome project was completed, many hailed it as the beginning of a golden age: all sorts of physical and mental illnesses would be linked to specific genes and a bright light shone on human suffering. But a decade passed and people were still being tormented by cancer, schizophrenia, etc. In an interview, Eric Green, director of the United States' National Genome Research Institute, even remarked, "I feel bad if our enthusiasm and euphoria over completing the genome project was misinterpreted to mean cures 10 years later."
Things had proved more complicated than expected. Rather than each disease originating in a single gene, most are caused by multiple genes. These interact both with one another and with the environment. This is not true of all disease, however. The BRCA1 and BRCA2 mutations, for example, are known to cause breast and ovarian cancer. Indeed, these mutations became famous in 2013 when the actress Angelina Jolie opted for a mastectomy and oophorectomy (ovary removal) after testing positive for them.
The genome project also improved our understanding of cystic fibrosis. This affects mainly white children (about one in 2,500), making their body fluids thicker than normal. As late as the 20th century, it was still being detected by touching a baby's forehead with the tongue to see if its sweat was salty. Today, we scan the child's DNA. Cystic fibrosis is caused by a faulty gene located on chromosome seven. Once the mutation is spotted, prognosis and treatment can then be worked out.
Such complications also spawned the new discipline of epigenetics. An epigeneticist studies how DNA expresses itself and how genes switch on or off. Stress, trauma, even diet and exercise, can influence gene expression. If scientists could find a way of altering these, switching the good ones on and the bad ones off, then theoretically we could cure cancer, prevent obesity, slow the aging process, and numerous other things.
Of course, such work has not come to an end. Critics talk as though we tried and failed. In reality, we are merely fumbling around at the beginning.
Take cancer, the "emperor of all maladies," as Siddhartha Mukherjee called it. It had long been known that certain cancers run in families. For generations family doctors had noted how a daughter would develop breast or ovarian cancer like her mother. Today, someone whose father, uncle, and grandfather all died of prostate cancer, for example, could ask for a genetic test.
If someone does have a specific cancer-causing mutation, they can have part of their body literally removed, as in the Angelina Jolie example. Others opt for regular screenings, increasing the chances of catching it early. And if they develop the disease, treatment can be shaped to fit the cancer. Indeed, we can now make a genetic profile of someone's cancer. Some are even working on vaccines. Dr Pramod Srivastava, a researcher at UConn Health, for example, is trying to create a personalized ovarian cancer vaccine.
Srivasta is using genomics (the study of genes and how they work) in his quest. As he says himself, "previous personalized cancer vaccines acted on faith; with genomics, we can actually know how each patient's vaccine is unique." Genomics is likely to prove especially helpful in treating rare genetic disorders. Diseases with strange, scary names like "FAM Hypercholesterolemia" and "Fragile X syndrome," derive from our genes. For such diseases, genomics offer real hope.
The human genome project also means better drugs. Using their knowledge of the human genome, scientists will soon create drugs that treat a disease by changing the way a gene works. Since your genes affect the way you react to a particular drug, different versions of that drug could be matched to an individual's genetic make-up.
Even transplants will be improved. The body is constantly threatened by bacteria and viruses. To defend itself, it makes use of an immune system. Special chemicals known as antibodies attack such invaders. Unfortunately, they also attack cells transplanted into the body from a donor.
All cells carry tiny markers on their surface, which are determined by their genes. These markers identify the cell as either "self" or "foreign." The immune system ignores the self cells and destroys the foreign ones. In the future, scientists hope to use their knowledge of genetics to enable transplants without rejection. Today, many transplant patients have to take anti-rejection drugs for the rest of their lives.
Then there is so-called "gene therapy." Imagine you are driving home one rainy evening and your car judders to a halt. A mechanic is called and identifies some broken pipe or plug. He replaces it and away you go. Gene therapy involves something similar. A faulty gene is identified and replaced with a healthy one.
In the future, new technologies, such as DNA microarrays, should help us understand more diseases. Once the faulty gene has been identified and replaced, it will produce the correct protein, make the cell work properly, and rid the individual of disease.
Take SCID, for example. This stands for "severe combined immunodeficiency disorder" and is caused by a single gene mutation. Victims become ill very easily. Indeed, a child with SCID must be isolated in a protective bubble. Some patients with this disease have already been treated via gene therapy.
First, cells called lymphocytes are removed from the patient's bone marrow. Incredibly, scientists then use a modified virus to carry a normal version of the gene back into the bone marrow cells. Viruses invade our cells, which is why they sometimes cause cancer. Scientists harness this to do good instead of harm. Once inside the body, the cells multiply and produce normal lymphocytes. Lymphocytes defend the body against disease, enabling the SCID patient to mix in the real world once again.
No one really knows what effect the Human Genome Project will have on medicine, but even the most pessimistic admit there will be effects. After all, human beings now have the recipe for life in their hands.