Genome research changes treatments

In 1940, the life expectancy of American males of all races was 60.8 years, while females lived 65.2 years on the average. By 1996, these figures had increased to 73 years and 79 years, respectively. The primary cause for this increase in life expectancy since WWII is unarguably the great advances that have been made in the development of drugs for hosts of formerly fatal diseases.

Yet there is a downside, according to Marc Wortman in the January-February 2000 issue of Technology Review. Medicinals are currently developed using a “one-size-fits-all” theory, meaning all sufferers from a specific illness are given the same drug to cure it. The result likely will be a cure in the vast majority of cases, no effect in some others, and an adverse effect, perhaps even fatal, to a very few. Wortman cites a 1998 study in JAMA that estimates 2.2 million patients had adverse reactions to drugs in 1994 and 106,000 of this number died. Now a rapidly growing field of medical research called pharmacogenomics is giving hope that drugs may one day be tailored to each individual, making adverse reactions a thing of the past.

In 2000, the human genome, the 6-foot strand of DNA that makes up the working blueprint for a human being, was deciphered. This was a monumental task involving the sequencing of the more than 3 billion base units that make up the genome. The bulk of the genome is identical for all humans; however, there are tiny differences known as SNPS or “snips.” These variations might be as little as one base unit in every 1,000, yet they can make a great difference in how the individual reacts to a given medication.

Wortman illustrates this point by the use of an anti-cancer drug for acute lymphoblastic leukemia, a form of cancer that strikes 2,400 children annually. The drug used to treat this disease is highly efficient in most cases, but 10 to 15 percent of the children metabolize the drug either too quickly or too slowly. In the former, a standard dose of the drug is not around long enough to do any good while, in the latter, a fatal dose can build up. A genetic screen has been devised to see what level of medication is indicated before treatment begins. This type of test defines pharmacogenomics, which is the study of an individual’s genetic makeup and response to a given drug.

The task facing researchers in pharmacogenomics is daunting. SNPS make up less than 0.1 percent of the genome but play a dominant role in determining how humans differ from one another, including their reactions to drugs. Thirteen normally highly competitive companies formed a consortium that have found more than 1 million SNPS while Celera Genomics of Maryland has a SNPS Reference Database containing 2.8 million.

But finding SNPS is just a small part of the battle, for only a small number, perhaps in the low thousands, are thought to dictate how our bodies may react to drugs. It will require the genetic screening of thousands of patients, along with detailed health histories, before drug researchers can hope to match these minute differences in the genome to reactions to specific drugs. The thought of putting people’s health records and genetic histories in the hands of commercial interests scares many people. As an example of what raises justifiable fears, the British government last year gave insurance companies the go-ahead to set premiums on the basis of genetic screening tests such as for Huntington’s disease.

As an example of the type of test now under way, Genaissance Pharmaceuticals is studying Lipitor, a cholesterol-lowering drug whose sales are $4 billion a year. Genaissance is collecting data on patients whose cholesterol drops or stays the same, and those who have had a bad reaction to the drug and then match the result to their genetic profile. The hoped-for outcome, said Wortman, is an optimal match between patient and drug.

Pharmacogenomics also will dramatically alter the role of the physician, said Wortman, who will in the future look at a patient’s genetic profile, the drugs available to treat a particular ailment, and then use a computer to optimally match the two. Eventually, physicians may even begin treatment based on a person’s genetic profile alone before symptoms have appeared.

Clair Wood taught chemistry and physics for more than 10 years at Eastern Maine Technical College in Bangor.