The Genetics of Immunity – Questions from Grandview Heights School

Earlier this week, I had a conversation with John Chase’s Science 9 class in Edmonton, Canada. We recorded the whole thing via google hangouts (the video is posted below), but we ran out of time and there were a lot of questions that the students had that I didn’t get to, so I thought I’d write them out.

From Abrar: “Is there a difference between genetic modifications in humans and animals? What are possible improved characteristics if a human were to be genetically modified.”

Humans ARE animals, so in principal, the process and the techniques are the same. The major difference at this point is a matter of ethics. We can do experiments on non-human embryos for instance. Genetically engineering a single cell that will give rise to a whole organism is much easier, since that cell will replicate all of the DNA-level changes that are made. Once a person is grown, trying to change the genes in all of that person’s cells is much more difficult.

But genetic engineering of people is already happening. Using engineered viruses, we can presently insert new genes into people. This approach carries a number of risks, so this form of engineering is only being done in order to treat diseases that are already life-threatening, but as we get better at understanding and mitigating the risks, this technique will be used for much more.

Probably within the next 10-20 years, we’ll have the technology to customize our offspring (if you’ve never seen the movie Gattaca, you really should – it’s over 15 years old now, but holds up incredibly well). Whether or not we decide to allow that as a society is a different question.

From Vincent: Is it possible to change multiple genes or cells to make humans supernatural and make them “Super Humans”? At the same time will we be able to use this for “Super soldiers”?

Not yet, but in principal – yes. Sort of. It really depends on what you mean. We’ve been selectively breeding plants and animals for desired traits for a long time, and these traits have genetic components. When we learn more about what genes influence certain traits, we could in principal engineer the genes of people to make them more able to build muscle, or have higher oxygen content in their blood so they get tired less quickly. If we started before birth, we could engineer people to grow taller etc.

But it’s important to remember that we can’t genetically engineer people to have traits that don’t presently exist. For instance, there’s no gene or set of genes that would enable people to breath fire, or have skin that contains kevlar to resist bullets.

300px-Ang2

“Archangel” from Marvel comics. Click for source.

Also, processes that require organized tissue growth are much much much more difficult to understand and control. Let’s say for instance you wanted to create the X-man character Archangel, who has wings sprouting from his back. Birds have wings, so in principal, there are genes that control their development that you could potentially engineer into people. However, there are probably hundreds of genes that control that development, all of which have to act together in incredibly coordinated ways. We don’t currently understand exactly a bird’s genes direct the development of the wing, let alone how to get human cells to follow the same developmental pattern. Even if we could figure that bit out, would a human with wings be aerodynamic enough to fly? Would we have to engineer all the bones in the body to be filled with air sacs like bird wings (that would be much harder to do unless it was started from birth)?

I believe that a lot of things will one day be possible with bioengineering. I think we’ll one day be able to grow seeds from buildings and manufacturing will be more like farming. But all of this is a loooooong way off.

 From Chikku: We learned that you can genetically engineer organisms and take the more desirable variations from different organisms. What happens at the DNA level for this to happen, like how does the organism change?

The answer to this question could take up several blog posts, depending on the level of detail desired, but the overall answer is that DNA code is inserted into the genome of the recipient. Usually the way that this is done is by using viruses (or in plants, bacteria) that have evolved to insert their own genes into their hosts. We can take advantage of this naturally occurring genetic modification done by pathogens to insert DNA that we care about.

The key is that the desired trait has to be coded for by a gene in the first place. Once the gene is in, the protein coded for by the gene can be expressed, and that protein will perform its function in the cell. For instance in plants, one genetic modification is for the plant to produce a protein toxin that was originally discovered in the bacterium Bacillus thuringiensis. The toxin is deadly to certain insects, so once the plant makes it, they gain the trait of being resistant to those insects. Other genes might code for proteins that increase growth rate of a particular part of the plant, or allow the plant cells to use water more efficiently.

However, as I mentioned above, some traits are incredibly complex, requiring many genes and complex regulatory pathways, and others are determined or at least shaped by the environment.

From Fawaz: “When you clone an organism, is there any chance of variation to occur, or will their genome be exactly identical to their ‘twin?’”

Twins are a good way to think about it. There is a chance of variation, but their genome will be identical. If you know any identical twins, you know that they can have very different personalities, and even look a bit different (parents of identical twins can usually tell them apart), even though their genomes are identical. Some of this variation is due to effects of the environment on development, some of it is due to random chance (unlike a computer program, a lot of what goes into the development of a biological system is governed by chance).

There’s also a lot of complexity due to something called “epigenetics,” which is too complicated to talk about in such a limited space, but you can read more about that here. Also, as I mentioned during class, the receptors of your adaptive immune system are generated randomly, so twins (and clones) will end up with variation in their responses to infections.

Also from Fawaz: I learned that stem cells occur in the bone marrow, where blood cells are created through the process of hematopoiesis, adipose tissue (lipid cells), blood via pheresis, and the umbilical cord post-birth. I also learned that autologous stem cell harvesting is least likely to be rejected by the immune system. Are there any other ways of obtaining stem cells? Artificial? Has there been a case of immune rejection of autologous stem cells? Is stem cell harvesting harmful to donors? Can stem cells be preserved or do they lose their “effect” over time?

All tissues are regenerated by stem cells, but what biologists mean when we say stem cells is somewhat different than the popular understanding of stem cells. Some stem cells (like embryonic stem cells) can give rise to every type of cell found in the body. Some, like the hematoapoietic stem cells you mentioned can only give rise to a limited population of cells (in the case of bone-marrow stem cells, red and white blood cells).

Some stem cells can be harvested from adults – you can donate bone-marrow for instance. This process can be a bit unpleasant – they used to drill into your hip bone and insert a long needle – now you can be given drugs that cause you to make excess bone-marrow stem cells that leak out into your blood (so they can draw blood and harvest them), but those drugs can make you feel quite ill. There isn’t really any long-term damage from these processes though.

The most desirable stem cells are those that can produce any type of tissue (these are called “pluripotent”), but as of now, those can only be harvested from embryos – once you’re an adult, you don’t have any that we’re aware of. There are people working on making these artificially from non-stem cells by activating a set of genes that reverts a cell into a pluripotent state, which has the added advantage that these stem cells would share your genome. As far as I’m aware, it shouldn’t be possible to reject an autologous transplant, since the genetic information would be identical.

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I think I answered the other questions in the video, but if there are any others (or if you have new questions based on what I wrote here), please don’t hesitate to ask in the comments.

What’s Eating Us?

My first post for the new blog at Scientific American is up!

Among the potential symptoms of infectious disease, perhaps none is unpleasant as diarrhea. For those of us in the western world, the unpleasantness rarely exceeds a couple of uncomfortable days in the bathroom, but for most of the developing world, infectious diarrheal illness is a significant public health threat. An estimated 2-4 billion episodes occur worldwide, and these are most prevalent in infants, whose stomachs are not as acidic and are therefore less able to kill of potential invaders on the way in. Excessive effluence (I will quickly run out of euphamisms for this) leads to rapid dehydration, sometimes so quickly that fluids cannot be replenished quickly enough without an IV. Adding insult to poopy injury, in many cases the source of water used to combat the loss of fluids is the same contaminated source that carried the infection in the first place, introducing fresh new invaders to replace the ones that are being expelled.

 

Check it out!

New #SciAmFood Blog is Here!

Drip-Irrigation 200x200I’ve joined a new food-related blog at Scientific American called Food Matters, where I’ll be discussing the infectious diseases, microbiology and public health-related aspects of food consumption. Check out the amazing group of authors contributing to the blog, grab the RSS (it’s broken as of this moment, but should be online shortly), and stick around for all your food-science needs.

I’ll still be writing here at RWaL (actually, I’ll probably be writing more here since I had to close up shop at We, Beasties) so don’t go away!

 

Microbial Metabolic Engineering Talk

engineeringcells-imageA couple of weeks ago, I gave a talk for Science in the News, a graduate student group at Harvard that aims to bring science to a wider audience. My talk was titled “Living Factories: Engineering Microbes to Make Useful Molecules,” and it’s about how scientists can engineer microorganisms to do cool stuff like make drugs or biofuels.

I’ll likely be posting a lot about this in the future on RWaL – it has many implications for public health, as it can be used in treatments for disease, and since climate change and energy policy will have vast and lasting impacts on human health in many different ways. This “metabolic engineering” is also what I plan to do in my post-doctoral research, so I’ll be steeped in the literature for some time to come.

We broadcast the lecture using Google’s hangouts on air feature, so the lecture is live on Youtube now – jump to about 22 minutes in to hear the actual lecture. If you have any questions that didn’t come up during the talk, let me know in the comments!

 

Science Denialism and Relative Risk

In the last few days, a confluence of posts around the bloggosphere on science denialism from vaccines to GMO to global warming has led me to consider an important question. Does it even matter if the denialists are right? Let me explain…

At his blog on Discovery, Keith Kloor writes:

Although our improved health and longevity are due to science, we moderns in the industrial world increasingly blame diseases (some that are wholly psychosomatic) on technologies that we owe our less-diseased, better-living lives to. What many of us are most afflicted with today are assorted fears and dreads stemming from the very advances that have made us the wealthiest, healthiest humans of all time.

This, in response to the vaccine-related rantings of  Robert F. Kennedy Jr, who believes that thimerosal, a preservative sometimes used in vaccines, is driving the epidemic of autism, despite mountains of data that it doesn’t, and the fact that thimerosal has not been in childhood vaccines for over a decade. Laura Helmuth, the science editor at Slate, recounts an epic phone conversation with JFK Jr. on the same topic.

Then I clicked on a link to a piece by Michael Specter about nuclear power, and the fact that if you’re an environmentalist concerned about climate change, you should probably embrace nuclear power. He notes:

But life is about choices, and we need to make one. We can let our ideals suffocate us or we can survive. Being opposed to nuclear power, as Rhodes points out, means being in favor of burning fossil fuel. It’s that simple. Nuclear energy—now in its fourth generation—is at least as safe as any other form of power. Fukushima was a disaster, but was it worse than the fact that our atmosphere now contains more than four hundred parts per million of carbon dioxide, a figure that many climate scientists believe assures catastrophe? Sadly, we may soon find out.

In that piece, he links to an article about the E. coli outbreak in 2011, which was due to shoddy growing practices in the organic industry:

David Mastio of the Washington Times, for instance, points out that twice as many people have now died from eating organic food than died in the Gulf of Mexico oil rig explosion and the nuclear power plant meltdown in Fukushima, Japan combined. Pajamas Mediawarns more succinctly, “Eat Organic and Die.” But the powers-that-be in the organic industry are already pushing back, attacking their detractors personally instead of responding to their genuine concerns, a tactic to which I have grown accustomed over the years.

So here we have three issues of great concern for public health, all of which are informed by settled science, but are nonetheless politically polarizing. Science tells us that vaccines do not cause autism, that nuclear power can be safe, and that whole mess about GMOs vs organic (let’s leave that alone for now).

As Specter notes, the question is not nuclear power or not, the question is nuclear power or fossil fuels. Similarly, the question is not get vaccinated or don’t, the question is get vaccinated or be at risk for debilitating or deadly diseases. These articles led me to wonder, even if we assume that the science-deniers are correct, would that change the answer to the public health question?

The CDC says that 1 in 88 children are diagnosed with autism, and the website Autism Speaks says that this is a 10-fold increase over 40 years. Let’s pretend for a moment that the anti-vaccine folks are right (they’re not), and let’s be incredibly generous and say that all of the increase in autism is due to vaccination. Since about 4 million children are born each year, that means there are about 45,000 children/year that will go on to be diagnosed with autism at some point along the spectrum.

Before the advent of the pertussis (whooping cough) vaccine, there were on average about 150,000 cases of pertussis in the US each year. Assuming that case load would increase roughly with population, without vaccination, we would have about 400,000 cases/year.

Source: CDC

The CDC says about 1.6% of pertussis infections are fatal, so in a world without the pertussis vaccine, roughly 6400 people would die from pertussis each year, most of them children.

Making a choice between 6400 children dead and 45,000 kids with autism might be a tough choice. I’m honestly not sure what I would choose, But then add in polio (population-adjusted 2,000 deaths/year, 26-40,000 cases of paralysis), measles (almsot 1,000 deaths/year), pnemoccoal disease (~10,000 deaths/year, not to mention deafness and seizures), diptheria (30,000 deaths/year), and the calculus doesn’t seem that hard.

And I didn’t even mention rubella:

In 1964-1965, before rubella immunization was used routinely in the U.S., there was an epidemic of rubella that resulted in an estimated 20,000 infants born with CRS, with 2,100 neonatal deaths and 11,250 miscarriages. Of the 20,000 infants born with CRS, 11,600 were deaf, 3,580 were blind, and 1,800 were mentally retarded.

We know that vaccines don’t cause autism, but for the people that can’t be convinced by evidence, maybe they can be convinced by math.

The trouble, as Laura Helmuth writes

You’re allowing your healthy child to be injected with some mysterious substance to prevent a disease that—because vaccines work so well—you have never even seen.

 

Union of Concerned Scientists Response to My Piece in SciAm

On Thursday, I had a post published on Scientific American’s guest Blog about claims that genetically modified food crops could contain allergens. In it, I am critical of the Union of Concerned Scientists (a science advocacy and policy organization), for what I read as misplaced opposition to genetic engineering:

The UCS’s concern about the dire state of our food system is well-founded, and I applaud their efforts to get out in front of the policy debate. There’s just one problem: they oppose using all of our technology to help combat this problem. Specifically, I’m talking about genetic engineering (GE) and genetically modified organisms (GMO)

Via e-mail and on twitter, some folks from UCS made it clear that they believe I’ve mischaracterized their position. They haven’t given me permission to publish the e-mails, so I won’t, but I’ll try to paraphrase. I was told that UCS does not oppose all uses of GMOs, but they believe that current policy does not do enough to regulate new GE varieties, that GMO companies have too much power to push past the regulation that does exist, and that there are alternatives to GE that should be pursued more aggressively. You should check out their website to read their position for yourself.

I largely agree with their position on agricultural issues – there isn’t adequate regulation of new crops, large industrial farms have too much influence, and we’re too reliant on monoculture (growing a single variety of a single crop year after year). However, none of these problems are unique to genetically engineered crops, and I think the fact that UCS has singled out GE as a problem confuses these issues. If GE crops were banned tomorrow, all of these same problems would remain.

I should be clear that I support UCS generally, and their work on agriculture specifically. Their roadmap for healthy farm policy is a wonderful and succinct explanation for what’s wrong with the way we currently grow food, and policy proposals to make it better. But GE is a technology (among others) that can help us make it better. Yes, they should be regulated, but so should new varieties produced by techniques like mutation breeding. Yes, we need to move away from monoculture and industrial farming practices, but that’s true of GE and organic farming alike.

Genetic engineering, like any other technology can be used for good and for ill. It can be helpful and it can be dangerous. New regulations and policies should be technology-neutral, and focus on outcomes.

This post was also published on We, Beasties

Nuance and Truth, Obesity Edition

For many years, excess weight was seen as uniformly bad, but some recent studies out of the CDC suggest that the reality is a bit more nuanced. As Virginia Hughes writes in Nature:

…many researchers accept Flegal’s results and see them as just the latest report illustrating what is known as the obesity paradox. Being overweight increases a person’s risk of diabetes, heart disease, cancer and many other chronic illnesses. But these studies suggest that for some people — particularly those who are middle-aged or older, or already sick — a bit of extra weight is not particularly harmful, and may even be helpful. (Being so overweight as to be classed obese, however, is almost always associated with poor health outcomes.)

Hughes highlights the biggest problem with the emergence of this data: how should doctors and the public health community talk about nuanced data? It’s abundantly clear that obesity is a public health problem, and one that’s growing, and some scientists worry that walking back the dire warnings in the case of being moderately overweight may be confusing and give people an excuse to ignore achieving an ideal weight.

Some public-health experts fear, however, that people could take that message as a general endorsement of weight gain. Willett says that he is also concerned that obesity-paradox studies could undermine people’s trust in science. “You hear it so often, people say: ‘I read something one month and then a couple of months later I hear the opposite. Scientists just can’t get it right’,” he says.

OBESITY_PARADOX_graphI don’t know this field particularly well, but based on the graph provided in the piece, it seems like the only age group in which this “paradox” really exists in people age 70+. The piece also notes that there are plenty of potential confounding factors (smokers tend to be lighter for instance), but let’s just say for the sake of argument that this paradox really exists and the message that the data tells us about weight gain is indeed murky. What’s a doctor or public health professional to do when it comes to informing patients about the risks of being overweight?

 

There are a couple of potential responses that scientists in Hughes piece put forward. On the one hand, we can tell patients everything and allow them to make their own choices. On the other hand, we can push the message that being overweight is bad, without nuance, dismissing the studies that say otherwise as being poorly done or being inconclusive enough to warrant ignoring them in the interest of a consistent message.

The former idea seems to be the most ethical, but knowing what we know about human behavior, it seems like there’s a decent chance that regular people will be unable to grasp the nuance, and it will end up muddying the message on the very real public health crisis that obesity is. Is laying out all of the information really the ethical thing to do if it will lead to more disease and lower life expectancy for more people? Is it ever ethical to withhold true information in the interest of the greater pubic good (I’m not wondering about directly lying to people, just about being selective about certain things)?

I’m asking these questions because I don’t know the answer – I can see both sides. Sometimes telling people the whole truth leads to misunderstanding that leaves them with a less-true picture of reality.

(h/t Razib Kahn)

TB and the Writing on RWaL

I would like to offer a general introduction to my public health and scientific interests that will be shared on our new blog Red Wine and Lariam.  In light of the title of this post you should know it is not about TB, the homonymous infectious disease that significantly predates the use of my initials.  Though, I will touch briefly on that pernicious bug in a later blog entry.  As I noted in my last post, I will be sharing a brief account of how my first trip to Sub-Saharan Africa led to the naming of this blog and a little bit about my view that we live in a microbial world.  The second half of this post is going to consist of a survey of the general topics that I expect Kevin Bonham (my collaborator on this blog) and I will be blogging about in the future.  Feedback on any subject is welcome.

After returning from Africa I was recounting to Kevin the completely surreal nature of finding myself deep in the bush of rural Malawi.  I was trying to express how at the time I felt I was pushing the limits of my capacity to process the incredible beauty around me simultaneously juxtaposed against the apparent burdens of human disease.

It wasn’t unusual at the time to try and consciously strike the right balance between my mix of morning coffee from Mzuzu, evening red wine from Stellenbosch, and my weekly dose of lariam.   Continue reading

Standing on the Shoulders of Giants

In my last conversation with my non-blood related biological brother, Kevin Bonham (my collaborator on this blog), he impressed upon me the virtue of viewing the benefits of pushing the envelope of our public scientific sharing by way of employing the ‘paying it forward’ philosophy.  He quoted Isaac Newton, and to a lesser-known extent a variant of a phrase attributed to Bertrand of Chartres, when he told me, “If I have seen further it is by standing on the shoulders of Giants.”  In that moment Kevin gave me a greater insight into the magnitude of the building blocks we stack as scientists.  Many of these blocks are laid upon ancient foundations. Today the deluge of scientific knowledge is flooding our journals, classrooms, social media and many of our conversations shared over coffee.  In the modern era, scientists are at best spreading a thin veneer of novel insight over the mountains of knowledge that came before us.

It is in the vein of this insight that I begin my public sharing in the domains of science and biology.  For just over 20 years I have had the good fortune to be surrounded by brilliant people at institutions and organizations that have opened the doors to my study of life as a biologist.  My current academic study in public health is focused on epidemiology, the study of ‘what is upon the people’ in our communities.  The goal is to understand the conditions that surround disease and health.  I have spent all of my adult life, since the age of 17, immersed in searching for the connections between the highest orders of life to the lowest.

Scripps Institution of Oceanography, University of California, San Diego

The quest has brought me from trying to understand the thresholds of human disease to studying the fundamental physics of the molecular interactions of the smallest known organisms and particles that interact with living things.   Continue reading