The Human Genome an Imperative Discovery Tool

Pardis Sabeti: Well, so it’s basically a method by which you can look in the human genome and let it-- It’s a discovery tool. Right. You look in the human genome and you see what has emerged, what’s been- become really common and prevalent and therefore must be important for our survival, and the things that you find are interesting. A lot of them we like to say are very-- it’s skin deep so a lot of them is to do with pigment. When you look in Europe and Asia it’s the lighter skin.

Those are things that have become very common. It looks like hair in Asia so hair and sweat glands in the Asian population have been under evolutionary pressure. So a lot of things that just allow you to interact with the environment that seem to be under potential pressure and then lactose tolerance is another big one so the ability to drink milk. Again it’s an effect as our nutrition, as our sources of food change, our metabolism changes and how we use those resources. So those are the kinds of things that we find but one of the- to me the most interesting with my background in- sort of clinical background and MD is that the other thing that’s very strongly under selection is things that are known to protect from malaria and things that seem to be involved with infectious disease.

So it makes sense that as we’re moving to different environments and climates we’re changing our sort of skin and our sweating patterns to deal- to thermoregulate and deal with the sort of summery pressure. As we change our- domesticate plants and animals we are changing our metabolism and what we’re using as nutrient resources and as we deal with lots of infections so parasites, bacteria, viruses that are interacting with us all the time we need to survive. And so when I was looking through the genome I kind of honed in on-- Originally, I saw- I was developing the test looking at genes that were protected from malaria, seeing these kinds of patterns, and then as you look through the genome the things that protect from malaria seem to be evolving.

This is all very preliminary but it looks like a bunch of genes that are involved with Lassa hemorrhagic fever, which is a hemorrhaging fever that people get, also seem to be under evolutionary pressure. So it’s kind of pointing me to pathogens are a very important evolutionary pressure to humans and what’s very interesting is that what’s so interesting about pathogens is they are themselves changing so rapidly. So we see how we evolve and adapt to them but they are also continuing to evolve and adapt to us so it’s this moving target and their genomes are much like ours and we can study them in the same way and see how they survive.

 

Question: How does this help humans?

 

Pardis Sabeti: So as we look in the human genome we look to see what’s evolving and what’s protected from- and the things so far that we’ve identified important in infectious disease we’ve-- Malaria is when we understand a lot so we can see where those genes that protect from malaria seem to be under strong evolutionary pressure, and the kinds of things that we see is in the gene hemoglobin, the sickle cell mutation, G6PD deficiency.

You see a lot of things that are involved in immune response or T-cell response and so you see both red blood cell because malaria invades the red blood cells so both receptors on a red blood cell and things that are important in the constitution of the red blood cell under strong evolutionary pressure and also things important in the immune system. So-- And one of the other genes is CD36 which is a receptor on endothelial cells so we see how both the immune system and the red blood cell are very important in malaria pathogenesis and that genes that are within those- sort of within the immune system and red blood cells are often under natural selection for protection from malaria.

 

Question: How do you distinguish between natural selection and randomness in gene mutation?

 

Pardis Sabeti: So that’s the process by-- So what’s nice is that we have a lot of candidates that we already know to be functionally important. Right. So we can look around those and that’s originally when I was developing the test I was. I was looking around genes that I already knew that were protected from malaria that we’d have an expectation that they would be under natural selection. Right. So they cause resistance to malaria and malaria’s been around for a long time and that you might expect to see them rise through the population. So that’s basically the test that I was working on is about that.

It’s about distinguishing just a random event and a random mutation that’s common in the population versus something that was sort of became prevalent too rapidly to happen by chance alone. So what we do is we go through and we look across the genome and we look for things that are very prevalent and things that are very young and we have a way- a threshold of saying this is too young to have become this prevalent by chance. And so it hasn’t been around long enough that it just sort of randomly got to this prevalence.

 

Question: Why do some people contract malaria and die and others not?

 

Pardis Sabeti: Well, we do know part of-- We do-- We know part of the story as to why some people get malaria and live and some people get malaria and die so there are-- Like I said, malaria is a very complex organism and the way that it invades and affects and it causes lots of different symptomologies like cerebral malaria or severe malarial anemia. There’s a lot of interactions that are going on with the host, with the human, and so we don’t understand every aspect of the disease but we do know some of the mutations that allow people to survive and we understand partly how that works. And again those have to do with things that are expressed in red blood cells or they’re important for red blood cells and things important in the immune system.

Well, actually I have a great group already. I have some-- I-- Harvard is a great place. There’s a great community around and I was already at- between MIT and Harvard at the Broad Institute so I had a lot of connections so I already have a very good core group of students and staff working with me, and essentially kind of-- one of-- We talk about what are the core principles that the lab does and what does everybody know, what are the core fundamental information that they have, and our lab is just based around methods, methods for understanding natural selection and important things in the genome.

And so what we work on is we work on developing better methods to study natural selection in humans and in malaria and other pathogens and better ways of understanding relationships between physical traits that we see and the genetic variation in the genome. So basically everyone in my lab is very method driven. How do we do this better? How do we understand this better? But then the things that we study is we do study human evolution so we continue to look at the human genome in different populations and see what’s important. And then we study the malaria genome s well and understand both how it evolves but also just trying to get the scope of what is the diversity out there in the malaria population, what’s going on, how well will our drugs work, how different are the different parasites in different populations, what is the evolutionary pressure for facing it. So essentially building is methodology and applying it both to humans and to pathogens.

And then the last one- the last kind of area of the group is this new thing, Lassa hemorrhagic fever, that we’re just recently studying, but it all ties in the same. Basically, it’s a very deadly infectious disease and it appears to be- have been in human populations for a very long time and have genes that are being spread through human populations to protect against it. So we’re investigating that right now and broadly investigating Lassa fever since it’s a very-- Who knows whether or not it’ll bear out, this-- these signals that we’re detecting for that pathway and for those genes that are important in the pathway, but regardless it just sort of pointed me to this disease that’s very understudied. So millions and millions of people are infected with it yet hardly any research funding is going towards it.

 

Recorded on: June 29, 2008

 

The Human Genome reveals a great deal about pathogens and the evolutionary history of humans.

Are we really addicted to technology?

Fear that new technologies are addictive isn't a modern phenomenon.

Credit: Rodion Kutsaev via Unsplash
Technology & Innovation

This article was originally published on our sister site, Freethink, which has partnered with the Build for Tomorrow podcast to go inside new episodes each month. Subscribe here to learn more about the crazy, curious things from history that shaped us, and how we can shape the future.

In many ways, technology has made our lives better. Through smartphones, apps, and social media platforms we can now work more efficiently and connect in ways that would have been unimaginable just decades ago.

But as we've grown to rely on technology for a lot of our professional and personal needs, most of us are asking tough questions about the role technology plays in our own lives. Are we becoming too dependent on technology to the point that it's actually harming us?

In the latest episode of Build for Tomorrow, host and Entrepreneur Editor-in-Chief Jason Feifer takes on the thorny question: is technology addictive?

Popularizing medical language

What makes something addictive rather than just engaging? It's a meaningful distinction because if technology is addictive, the next question could be: are the creators of popular digital technologies, like smartphones and social media apps, intentionally creating things that are addictive? If so, should they be held responsible?

To answer those questions, we've first got to agree on a definition of "addiction." As it turns out, that's not quite as easy as it sounds.

If we don't have a good definition of what we're talking about, then we can't properly help people.

LIAM SATCHELL UNIVERSITY OF WINCHESTER

"Over the past few decades, a lot of effort has gone into destigmatizing conversations about mental health, which of course is a very good thing," Feifer explains. It also means that medical language has entered into our vernacular —we're now more comfortable using clinical words outside of a specific diagnosis.

"We've all got that one friend who says, 'Oh, I'm a little bit OCD' or that friend who says, 'Oh, this is my big PTSD moment,'" Liam Satchell, a lecturer in psychology at the University of Winchester and guest on the podcast, says. He's concerned about how the word "addiction" gets tossed around by people with no background in mental health. An increased concern surrounding "tech addiction" isn't actually being driven by concern among psychiatric professionals, he says.

"These sorts of concerns about things like internet use or social media use haven't come from the psychiatric community as much," Satchell says. "They've come from people who are interested in technology first."

The casual use of medical language can lead to confusion about what is actually a mental health concern. We need a reliable standard for recognizing, discussing, and ultimately treating psychological conditions.

"If we don't have a good definition of what we're talking about, then we can't properly help people," Satchell says. That's why, according to Satchell, the psychiatric definition of addiction being based around experiencing distress or significant family, social, or occupational disruption needs to be included in any definition of addiction we may use.

Too much reading causes... heat rashes?

But as Feifer points out in his podcast, both popularizing medical language and the fear that new technologies are addictive aren't totally modern phenomena.

Take, for instance, the concept of "reading mania."

In the 18th Century, an author named J. G. Heinzmann claimed that people who read too many novels could experience something called "reading mania." This condition, Heinzmann explained, could cause many symptoms, including: "weakening of the eyes, heat rashes, gout, arthritis, hemorrhoids, asthma, apoplexy, pulmonary disease, indigestion, blocking of the bowels, nervous disorder, migraines, epilepsy, hypochondria, and melancholy."

"That is all very specific! But really, even the term 'reading mania' is medical," Feifer says.

"Manic episodes are not a joke, folks. But this didn't stop people a century later from applying the same term to wristwatches."

Indeed, an 1889 piece in the Newcastle Weekly Courant declared: "The watch mania, as it is called, is certainly excessive; indeed it becomes rabid."

Similar concerns have echoed throughout history about the radio, telephone, TV, and video games.

"It may sound comical in our modern context, but back then, when those new technologies were the latest distraction, they were probably really engaging. People spent too much time doing them," Feifer says. "And what can we say about that now, having seen it play out over and over and over again? We can say it's common. It's a common behavior. Doesn't mean it's the healthiest one. It's just not a medical problem."

Few today would argue that novels are in-and-of-themselves addictive — regardless of how voraciously you may have consumed your last favorite novel. So, what happened? Were these things ever addictive — and if not, what was happening in these moments of concern?

People are complicated, our relationship with new technology is complicated, and addiction is complicated — and our efforts to simplify very complex things, and make generalizations across broad portions of the population, can lead to real harm.

JASON FEIFER HOST OF BUILD FOR TOMORROW

There's a risk of pathologizing normal behavior, says Joel Billieux, professor of clinical psychology and psychological assessment at the University of Lausanne in Switzerland, and guest on the podcast. He's on a mission to understand how we can suss out what is truly addictive behavior versus what is normal behavior that we're calling addictive.

For Billieux and other professionals, this isn't just a rhetorical game. He uses the example of gaming addiction, which has come under increased scrutiny over the past half-decade. The language used around the subject of gaming addiction will determine how behaviors of potential patients are analyzed — and ultimately what treatment is recommended.

"For a lot of people you can realize that the gaming is actually a coping (mechanism for) social anxiety or trauma or depression," says Billieux.

"Those cases, of course, you will not necessarily target gaming per se. You will target what caused depression. And then as a result, If you succeed, gaming will diminish."

In some instances, a person might legitimately be addicted to gaming or technology, and require the corresponding treatment — but that treatment might be the wrong answer for another person.

"None of this is to discount that for some people, technology is a factor in a mental health problem," says Feifer.

"I am also not discounting that individual people can use technology such as smartphones or social media to a degree where it has a genuine negative impact on their lives. But the point here to understand is that people are complicated, our relationship with new technology is complicated, and addiction is complicated — and our efforts to simplify very complex things, and make generalizations across broad portions of the population, can lead to real harm."

Behavioral addiction is a notoriously complex thing for professionals to diagnose — even more so since the latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the book professionals use to classify mental disorders, introduced a new idea about addiction in 2013.

"The DSM-5 grouped substance addiction with gambling addiction — this is the first time that substance addiction was directly categorized with any kind of behavioral addiction," Feifer says.

"And then, the DSM-5 went a tiny bit further — and proposed that other potentially addictive behaviors require further study."

This might not sound like that big of a deal to laypeople, but its effect was massive in medicine.

"Researchers started launching studies — not to see if a behavior like social media use can be addictive, but rather, to start with the assumption that social media use is addictive, and then to see how many people have the addiction," says Feifer.

Learned helplessness

The assumption that a lot of us are addicted to technology may itself be harming us by undermining our autonomy and belief that we have agency to create change in our own lives. That's what Nir Eyal, author of the books Hooked and Indistractable, calls 'learned helplessness.'

"The price of living in a world with so many good things in it is that sometimes we have to learn these new skills, these new behaviors to moderate our use," Eyal says. "One surefire way to not do anything is to believe you are powerless. That's what learned helplessness is all about."

So if it's not an addiction that most of us are experiencing when we check our phones 90 times a day or are wondering about what our followers are saying on Twitter — then what is it?

"A choice, a willful choice, and perhaps some people would not agree or would criticize your choices. But I think we cannot consider that as something that is pathological in the clinical sense," says Billieux.

Of course, for some people technology can be addictive.

"If something is genuinely interfering with your social or occupational life, and you have no ability to control it, then please seek help," says Feifer.

But for the vast majority of people, thinking about our use of technology as a choice — albeit not always a healthy one — can be the first step to overcoming unwanted habits.

For more, be sure to check out the Build for Tomorrow episode here.

Why the U.S. and Belgium are culture buddies

The Inglehart-Welzel World Cultural map replaces geographic accuracy with closeness in terms of values.

Credit: World Values Survey, public domain.
Strange Maps
  • This map replaces geography with another type of closeness: cultural values.
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CT scans of shark intestines find Nikola Tesla’s one-way valve

Evolution proves to be just about as ingenious as Nikola Tesla

Credit: Gerald Schömbs / Unsplash
Surprising Science
  • For the first time, scientists developed 3D scans of shark intestines to learn how they digest what they eat.
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Mammals dream about the world they are entering even before birth

A study finds that baby mammals dream about the world they are about to experience to prepare their senses.

Michael C. Crair et al, Science, 2021.
Surprising Science
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