When he was 17 and in high school, Eric Seed fainted. In the emergency room, he was diagnosed with anemia, which can cause fainting spells, and for many years he thought that was the end of the story. About a decade later, in early 2010, he developed pneumonia and had blood tests. He glanced at the results and saw signs of anemia, as he expected. But the report also said his red blood cells were smaller than normal.
Syed was in medical school at the time, and immediately thought of some genetic conditions that could explain this finding. One such disease is thalassemia, which causes low hemoglobin levels, leading to anemia and other related problems. Laboratory examination showed that he was suffering from this genetic disease. This means he had a genetic mutation. Finally, he thought he had an explanation for the symptoms he’d been experiencing for years.
Except there was a catch. In the most common forms of thalassemia, people who develop symptoms have mutations in both copies of relevant genes. Those born with the most severe form of thalassemia require lifelong blood transfusions to get enough healthy red blood cells, and if the condition is not diagnosed soon enough, it can be fatal in early childhood. But Sayed’s laboratory results indicated that only one copy was affected, so he was considered a carrier of the disease, and could transmit it to his children, but he was not infected with it himself. According to conventional wisdom at the time, carriers of the disease were asymptomatic and, compared to someone suffering from the worst manifestations of the disease, appeared to be fine.
Syed now works in the Rare Diseases Program within the National Institutes of Health. He told me that since he first discovered he was a carrier of thalassemia, research has shown that people like him can experience health consequences. These include lethargy and fainting, symptoms that hardly reflect the classic manifestation of the disease, but which still have real consequences. Thalassemia is not unique. There are hundreds upon hundreds of known disorders for which carriers are thought to be safe; For an increasing number of these diseases, doctors and scientists now believe that being a carrier can lead to health problems. Syed said that many patients have guessed all along that being carriers of the disease could explain secrets related to their health. “It took a while for science to fundamentally catch up with this uncertainty.”
In these types of “recessive” conditions, people who show the classic manifestation of the disease have a pair of mutated genes. Our 23 chromosomes come in pairs that are essentially close copies of each other (except for the XY pairs). A person with one non-working copy of the gene was supposed to be protected by a second, working copy on the matching chromosome, which would provide a cover against any disease. Inheriting two mutated copies of a gene is statistically rare, so many families with carriers may not include individuals with the full version of the disease. As a result, a mutation can be passed from generation to generation unknowingly, without its carriers realizing the true consequences.
In October, researchers in Louisiana reported a case involving a college football player who developed heart palpitations during practice. The athlete was a carrier of sickle cell disease, one of the most common genetic disorders in America. Up to 10 percent of black Americans are sickle cell carriers. Since the 1970s, scientists have observed blood and heart complications in carriers of the disease after physical exercise, and a lawsuit that followed the sudden death of a college football player two decades ago led to widespread examination of sickle cell traits in college athletics. However, experts are still trying to understand the risks to carriers.
The Louisiana man survived, but researchers noted that he had a dangerous irregular heartbeat during training and would need heart surgery. The authors of the October paper stress that coaches and players need more education about the potential risks for carriers of sickle cell trait.
Experts who study cystic fibrosis, which is caused by mutations in the CFTR gene, also want more attention to the health complications that carriers of the disease can experience. As many as one in 25 Americans of European descent are carriers of cystic fibrosis, but many are unaware of their condition. For this disease, reports of symptoms in carriers go back at least several decades. Take infertility, for example. Almost all men with two mutated copies of the CFTR gene lack the vas deferens, and without these tubes, sperm would have no way out of the testicles. In the mid-1990s, scientists discovered a handful of cystic fibrosis Transportation companies Who lack the vas deferens, even though only one of their CFTR copies is mutated.
Cystic fibrosis carriers can experience other real health problems, such as dramatic sinus problems requiring multiple surgeries, pancreatitis, and possibly pancreatic cancer, which researchers have documented in research over the past several years. “We’ve always said being a holder of bachelor The cystic fibrosis mutation does not usually lead to health problems. “It usually doesn’t happen,” Michael Boyle, president and CEO of the Cystic Fibrosis Foundation, told me. However, we know, and perhaps have a greater appreciation than ever before, that being a carrier can lead to health problems for some. There are about 10 million carriers of cystic fibrosis in the United States alone, so if a small fraction of them have some degree of symptoms, this means that many people suffer from manifestations of the disease.
Questions about health problems for carriers go beyond well-known diseases such as sickle cell and cystic fibrosis. Consider xeroderma pigmentosum: People with two copies of the mutated gene are up to 2,000 times more likely to develop skin cancer than the average person. A 2023 analysis found strong evidence that some carriers were at higher risk of developing skin cancer. Up to 3 percent of carriers of hereditary hemochromatosis develop symptoms such as excess iron in their organs. People with Gaucher disease type 1 are at increased risk of developing Parkinson’s disease. Carriers of LIG4 syndrome have a version of the immunodeficiency, which causes life-threatening disease in the fully expressed syndrome.
For many of these diseases, having two mutated copies of a relevant gene generally means the disease will come to you. The presence of one copy still does not mean anything: many carriers of recessive genetic diseases do not seem to be any worse. It is estimated that one in 20 people, like Syed, is a carrier of thalassemia, but not all people with a version of the mutation suffer from anemia and fainting like him. It is not clear why some carriers of genetic diseases may be affected and others remain symptom-free. But “people who are thought to be carriers but have some symptoms of the disease may sometimes have a second mutation that is harder to detect,” Edward Neylan, chief medical and scientific officer at the National Organization for Rare Disorders, told me. “They may actually have two mutations.”
Being a carrier can have benefits. One theory as to why genetic diseases are so widespread is that having one copy of the mutated gene has some advantages. It is well understood, for example, that being a carrier of sickle cell disease offers some protection against malaria. Some have hypothesized that being a carrier of cystic fibrosis can protect against severe cholera, although the evidence for this theory is less. A 2023 analysis discovered that although two different copies of the SCN5A gene increase a person’s risk of developing severe heart rhythm problems, only one copy may actually do so. minimum A person’s risk of developing heart rhythm disorders compared with the general population.
Even when being a carrier of a particular disease is not beneficial in and of itself, knowing that you are a carrier can be helpful. For example, holders may want to Certain dry skin pigmentosum in extra efforts to avoid excessive exposure to sunlight; Some people with alpha-1 antitrypsin deficiency, who appear to have an increased risk of lung problems, may decide not to smoke. People with sickle cell trait may be advised to acclimatize before exercising at high altitudes.
For example, knowing that you are a carrier for cystic fibrosis may help guide your family planning decisions. (Even without the vas deferens, a person can become a father using sperm extraction and in vitro fertilization — which is what some cystic fibrosis carriers choose anyway, to avoid transmitting the disease.) But there are limits: Science is still not sure whether Trikafta, a relatively new drug that has remitted the disease in many people, will help with sinus or pancreatic problems in carriers of the disease. The drug is not approved for carriers of the disease either.
For Syed, knowing he had the thalassemia mutation – which can cause dizziness – made him feel worse about the difficulty he had with intense physical training, for example. He is relieved to know the possible cause of his fainting episode in high school. The discovery of the mutation in his genome gave him a fuller picture of his health. “Personally, that’s kind of what I saw, it kind of gave me more understanding,” he said.
