Before surgery, someone will hand you a form, and one of the questions on it is whether anyone in your family has ever had a bad reaction to anesthesia. It is a serious question. The answer can be a matter of life and death, which is why it is on the form at all. The reason it is asked about your relatives, rather than about you, is that until recently your relatives were the only way to guess at your genes.
A good question, asked the wrong way
The trouble is that most people have never had surgery, so they have nothing to report, and most families have never talked about it either. Worse, every dangerous reaction has to happen to someone first before anyone else in the family can be warned. So when your chart says “no family history,” it feels reassuring, but most of the time it just means no one has looked.
The information the form is asking for has been in your DNA the whole time. What has changed is that it can now be read.
Three drugs, three things that can go wrong
A typical operation uses three kinds of drug: one to put you to sleep, one to keep your muscles still, and one for the pain afterwards. Your genes have a say in how you respond to each of them, and in each case the consequences look different.
The one that puts you to sleep. The gases most commonly used to keep you under are safe for almost everyone, but in a small number of people they set off a dangerous chain reaction in which body temperature spikes, muscles lock up, and the heart races. About one in a thousand people carries a gene variant that puts them at risk, and most of them will never find out, because the reaction only happens if they are exposed to the trigger. Today, the ways people discover it are a relative having the reaction, a muscle biopsy, or having it themselves on the operating table. If the anesthesiologist knows in advance, none of that is necessary. They use a different drug, and nothing happens.
The one that keeps you still. Succinylcholine is a muscle relaxant given so the breathing tube can go in, and it normally wears off within about five minutes because an enzyme in your blood breaks it down. About one in a few thousand people are born with a version of that enzyme that barely works, and for them the same dose can last for hours, leaving them on a ventilator until it finally fades. These people are perfectly healthy otherwise, with no warning sign of any kind. Every hospital already stocks a different relaxant that does not depend on that enzyme, so the only thing missing is knowing which patients need it.
The one for the pain. Codeine does not relieve pain on its own. Your liver has to convert it into morphine first, and it is the morphine that actually works. The enzyme responsible is called CYP2D6, and five to ten percent of people carry two copies of the gene that do not function, which means their liver produces almost no morphine from codeine at all. They take the full dose and feel nothing, while their chart says they have been medicated. Other people have the opposite problem: extra, faster copies of the gene that turn a normal dose into far too much morphine. That is why codeine is no longer given to young children.
What this changes
Less than you might think, and that is good news. If you already know how your body handles these drugs, you tell your anesthesiologist at the pre-op appointment, they swap the drug, and that is the whole conversation. It takes about two minutes.
Anesthesiologists are careful people who work from guidelines, and guidelines for these exact gene and drug combinations have existed for more than a decade. The science is settled. The problem is purely practical: on the morning of your surgery, nobody in the hospital has this information about you.
Timing is the part that catches people out. Most operations are scheduled weeks ahead, but some are not, and appendicitis at two in the morning does not leave room to send off a sample. You cannot get your genome sequenced from a hospital bed, and no one will wait weeks for a result while you need surgery. This only helps if you already have the information before the day you need it.
It is worth being clear about what this is. It is information, not a diagnosis, and it is not a reason to stop or change any medication on your own. It is a reason to bring a specific question to your surgical team and let them decide what to confirm.
The same genes, the rest of your life
These enzymes do not only matter in surgery. They are the reason an antidepressant can do nothing for six weeks, the reason a cholesterol drug can make your muscles ache, the reason a blood thinner can take four appointments to get right. In one clinical study, nearly half of patients had an unusual version of CYP2D6 alone, and that is a single gene among many.
You sequence your genome once, and it answers all of these questions, both now and as the science improves. That is why we started Lifecode.
The next time that form asks about your family, you could actually know the answer.
Read your own genome.
Order your genome