If youre a long time reader of SciBlogs, you probably remember when James Watson was on the advisory board of SEED. You also probably remember he was removed from that position after he made some idiotic racist (and sexist) remarks.
In a wonderful bit of scientific lulz, Craig Venter recently compared his genome with that of James Watson and made some predictably astute observations about race, genes, and drugs.
‘Individual Genomes Instead of Race for Personalized Medicine‘ (its open access right now!)
Lets say you have a headache, so you decide to take some Tylenol. It dissolves in your stomach/intestines/etc, your headache goes away… But the Tylenol doesnt stay in your bloodstream forever! There is a family of enzymes, cytochrome P450, in all of your liver cells, breaking down the acetaminophen until it can be filtered out by your kidneys.
For a drug to work 24/7 (a heart medication, anti-depressant, etc), you need the drug to stay at a constant, therapeutic concentration in your bloodstream. You need to replace metabolized drug as fast as its being degraded, so you take doses every 6/8/12/whatever hours. BUT, you dont want to take too much, or else the drug might shoot past ‘therapeutic concentration’ and into ‘toxic concentration’. Everyone has heard of the grapefruit juice example– Grapefruit juice can inhibit some of the CYP450 enzymes, and you can accidentally OD if you take some drugs with grapefruit juice.
Things get trickier. Depending on genetic variations you have in your CYP450 genes, you might metabolize a drug too fast, or not be able to metabolize it at all. For example 5-10% of Caucasians have non-functional CYP2D6, so codeine has absolutely no effect on them (they cant metabolize codeine into morphine, SOOO glad Im not them). Some African Americans dont respond to first-line hypertension drugs, so a group has invented a ‘race based‘ alternative drug.
OMG BLAKS AND WHIGHTS R DUFFERENTZ! WATSON IZ RITE BLAK R DUMB!
Here is where we get back to Venter *grin*
Venter compared his CYP450 genes to James ‘Africans are dumb’ Watsons CYP450 genes.
Two white guys.
Venter has the ‘white guy’ alleles.
Watson has, ahem, ‘not white guy’ alleles. heh.
Venters point? Prescribing drugs based on ‘appearance’ of race is stupid. A ‘white’ person like James Watson can have ‘Asian’ CYP450 genes. ‘Black’ people from Ethiopia, Tanzania, and Zimbabwe can have different CYP450 profiles.
HACK THE PLANET. SEQUENCE EVERYTHING!
In one case study, a patient with heart problems was prescribed warfarin. Over the next 5 years, the man visited the hospital at least 20 times to have his blood samples taken as his doctor tried to establish the correct dosage. During this time, besides the inconvenience, the patient was at risk for hemorrhaging. Finally, in year 4, his DNA was genotyped, and he was discovered to be a poor metabolizer based on the sequence of his CYP2C9 gene, which is involved in metabolizing warfarin. Soon thereafter, the patient’s dosage was stabilized.
Because the cost of genotyping and sequencing has decreased dramatically in the past few years, we no longer need to guess the genetic makeup of an individual. With current technology we can definitively determine a million genotypes for an individual in a matter of days, and this will only improve as technology advances. Revisiting the patient on warfarin who was a poor metabolizer, we have no idea what color his skin was, and it does not matter–it was his genotype that ultimately mattered.
This is why I get so angry with people like Francis Collins, scared of everyone being sequenced. Sequencing everyones CYP450 profile will not only save lives, but improve the quality of life for all of us!