Does Hepatitis B Affect Human Gender Ratios?

Interview with Dr. Baruch Blumberg (Part I)

Dr. Baruch Blumberg, who served as the first Director of the NASA Astrobiology Institute, is one of the world’s leading experts on the hepatitis B virus (HBV). He was the 1976 recipient of the Nobel Prize in Medicine, for his discovery of the virus, and subsequently helped develop both the test used for detecting it and a vaccine to prevent its spread. Hepatitis B virus, a primary cause of fatal liver cancer, has infected some 2 billion people now alive worldwide and about 375 million remain infected. Blumberg is currently the senior advisor to the president of the Fox Chase Cancer Center and a professor of medicine at the University of Pennsylvania, both in Philadelphia.

Astrobiology Magazine’s Henry Bortman interviewed Dr. Blumberg about hepatitis B, his current research, and the role of viruses in the evolution of life on Earth. In this first part of a two-part interview, Dr. Blumberg discusses the possible role of the hepatitis B virus in controlling the ratio between men and women in the human population.


Montage graphic: Astrobiology bridges the very small to the largest scales, the ancient past to the distant future.

Astrobiology Magazine (AM): What is the hepatitis B virus and how common is it among humans?

Barry Blumberg: Hepatitis B is one of multiple viruses that affect the liver and cause serious pathology of the liver. Hepatitis B is probably the first or second most common. About a third of the world’s population, more than 2 billion people, have been infected with it, and about 375 million are currently infected. Compare that to other pathological viruses, such as HIV, which causes AIDS – there are probably 42 million people who are currently infected.

Most people who get infected by viruses in general, and hepatitis B in particular, develop antibody against them, and don’t get sick. There are a variety of antibodies that they may carry, they indicate that they were previously infected. Many people remain infected, and that can be detected by a simple blood test. So there’s pretty accurate information on the number of people who are infected. About a third of the world has been infected. It’s one of the most common infectious agents in the world.

AM: Hepatitis B is known to cause liver cancer. What’s the relationship between the two?

BB: That process isn’t clear, and it’s one of the most important aspects of cancer pathogenesis right now, because it will tell you how viruses contribute to the cause of cancer – which happens commonly. A general answer is that the virus slowly leads to the death of cells, which means that there is more division of cells in order to replace those that were lost. Division of cells increases the probability that mutational events can occur that can contribute to the development of cancer.

There can be other factors in the environment that combine with these mutational events to increase the probability that the host of the virus, would go on to get cancer. In some of the lower animals that get cancer after infection with hepatitis B-like viruses, you see a connection with oncogenes, genes that are known to cause cancer. In humans, there’s probably some relation, but it’s not very straightforward. So broadly speaking, it’s the increase in the probability of mutational events due to the increased division of cells that adds to the risk of getting cancer.

There are other things that can contribute to the etiology of liver cancer along with HBV. Certain toxins are related to primary cancer of the liver and they may have an important role. And then there’s at least one other virus that also is etiologic, hepatitis C virus. That’s also quite common. There are probably a couple hundred million HCV carriers worldwide.

Transmission electron micrographs of virus and virus-like particles isolated from YNP.
Image Credit: Montana State University

AM: Hepatitis B appears to have a role in the determination of gender ratio at birth. It also kills more men than women in older age groups. Could you talk a little bit about that?

BB: Males are more susceptible to chronic infection than are females; males and females may both become infected at about the same rate, depending on their exposure to infection but males are more likely to become chronically infected than females. And people who are more chronically infected are more apt to go on to get chronic liver disease and primary cancer of the liver than people who are not chronically infected. But even among chronically infected people, males seem to be more prone to go on to pathology than females. Mind you, females do get these diseases, and do get cancer of the liver, but the ratio is higher for males compared to females.

Now what the mechanism is, that’s part of this interesting mystery. Whether it has something to do with differences on the X and Y chromosomes, or endocrinal differences, or similarities between certain male-related genes you find on the Y chromosome and the products of HBV genes, that’s conjecture. . But to my knowledge there’s no clear evidence that these hypotheses are supported by data. I think it’s fair to say that it’s not really understood. People don’t ordinarily look at male-female differences in respect to viral infections.

AM: There’s also a gender effect on birth rate?

BB: Yes. I should tell you, by the way, that what I’m telling you about this gender ratio is based mostly on data generated by our laboratory, going back more than 30 years – which requires validation, as all data does. Based on our data, parents who are carriers of hepatitis B virus have a lower birthrate – the technical term would be fertility – than parents who are not carriers of the virus. The lower birthrate is due to the birth of a smaller number of live female children. And as I’ve already said, infection also affects the gender ratio in older people, in that older male carriers have a higher probability of dying from chronic liver disease and cancer of the liver than do women.

AM: Why is it important to understand a mechanism like that?

A 3D structure of RNA.
Credit: SpaceDaily

BB: Practically, if you can understand this difference, there may be something you can do in a preventative or therapeutic way that builds on that knowledge. It’s also very interesting from the point of view of evolution. Because the ratio of males to females in a population is a major indicator of success in reproduction. Females are the rate-limiting step. You can have a lot of males, but the females are the ones that have to have the children, so it acts as a control on the number of children in a population.

AM: If the virus reduces the number of girl children, does it act as a population control overall?

BB: It probably contributes to it. It’s really hard to quantify that because there are other gender-related effects that are very large and that may overwhelm the effect of hepatitis B on the gender ratio. As you know, there’s something of a scandal about selective abortion, based on detection of gender prior to birth. In many places this is illegal; and in many places, if not most, it’s considered unethical to abort on the basis of gender. But, nonetheless, that happens. And that may have a bigger effect than any effect of the hepatitis B virus. Another factor is that very often in populations where people want to limit family size, but they also want to have boys, rather than girls, they will continue reproducing until they get the number of boys they want to have, and then they’ll stop having children . That is a social or psychosocial factor. And there may be other natural factors in the environment. But the effect of hepatitis B infection on the overall gender ratio in a population is one that we were able to detect.