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Inheriting Our Personalities

Research into our genes is revealing more evidence that our behavior and overall psychological state is influenced by deterministic biological factors. The chief area of interest in this regard is epigenetics, a fairly new development in the field. In brief, epigenetics encompasses the following:

The methyl group works like a placeholder in a cookbook, attaching to the DNA within each cell to select only those recipes — er, genes — necessary for that particular cell’s proteins. Because methyl groups are attached to the genes, residing beside but separate from the double-helix DNA code, the field was dubbed epigenetics, from the prefix epi (Greek for over, outer, above).

 

Originally these epigenetic changes were believed to occur only during fetal development. But pioneering studies showed that molecular bric-a-brac could be added to DNA in adulthood, setting off a cascade of cellular changes resulting in cancer. Sometimes methyl groups attached to DNA thanks to changes in diet; other times, exposure to certain chemicals appeared to be the cause. Szyf showed that correcting epigenetic changes with drugs could cure certain cancers in animals. 

 

Geneticists were especially surprised to find that epigenetic change could be passed down from parent to child, one generation after the next. 

That last part is the kicker, for it suggests that certains traits responsible for a range of characteristics can run along family lines. Hereditary issues are nothing new of course, but those typically pertain to health matters like heart disease or hypertension rather than rather than personality types (though in the case of mental illness there’s obviously an overlap).

What’s more, these epigenetic factors are influenced by the environmental and social conditions of the individual, which has important implications concerning the long-term consequences of traumatic events like war or poverty. 

According to the new insights of behavioral epigenetics, traumatic experiences in our past, or in our recent ancestors’ past, leave molecular scars adhering to our DNA. Jews whose great-grandparents were chased from their Russian shtetls; Chinese whose grandparents lived through the ravages of the Cultural Revolution; young immigrants from Africa whose parents survived massacres; adults of every ethnicity who grew up with alcoholic or abusive parents — all carry with them more than just memories. 

 

Like silt deposited on the cogs of a finely tuned machine after the seawater of a tsunami recedes, our experiences, and those of our forebears, are never gone, even if they have been forgotten. They become a part of us, a molecular residue holding fast to our genetic scaffolding. The DNA remains the same, but psychological and behavioral tendencies are inherited. You might have inherited not just your grandmother’s knobby knees, but also her predisposition toward depression caused by the neglect she suffered as a newborn. 

 

Or not. If your grandmother was adopted by nurturing parents, you might be enjoying the boost she received thanks to their love and support. The mechanisms of behavioral epigenetics underlie not only deficits and weaknesses but strengths and resiliencies, too. And for those unlucky enough to descend from miserable or withholding grandparents, emerging drug treatments could reset not just mood, but the epigenetic changes themselves. Like grandmother’s vintage dress, you could wear it or have it altered. The genome has long been known as the blueprint of life, but the epigenome is life’s Etch A Sketch: Shake it hard enough, and you can wipe clean the family curse.

I’ll leave you all to read the rest, as it’s very interesting. While research is still ongoing, there are several takeaways to keep in mind.

First, this finding reinforces the fact that many psychological pathologies — from mental illnesses to certain personality traits — are rooted in biology, which in turn is influenced by external factors such as how you’re raised, fed, etc. To this day, despite mounting evidence to the contrary, a lot of people continue to treat mental conditions as being determined by human will and discipline alone, rather than biology. 

Second, this explains why certain social and ethnic groups with a long history of oppression and mistreatment seem trapped in a cycle of poverty, violence, and other social ills. In addition to any lingering discrimination, there’s the possibility that each generation is carrying the epigenetic baggage of the preceding one, and in turn placing that upon their progeny. This drives home the importance of improving socioeconomic conditions for these groups, rather than simply writing off their pervasive problems as being exclusively cultural or social. 

The most important implication regards social and economic policy — if the harms (and benefits) that befall one generation extend well-beyond it, that means the consequences of systemic violence, domestic abuse, poverty, racism, and other negative conditions are even more dire. We risk entrenching these problems through a self-perpetuating cycle — a sort of generational momentum, if you will — that can only end once we acknowledge the importance of systemic and collective approaches to addressing societal problems. 

Needless to say, this will be a tough sell in our society, even though the timing couldn’t be more vital, given the advent of a new lost generation from our recent economic meltdown. 

Scientists Transform Skin Cells of Mice into Neurons

I’ve touted the remarkable medical potential of stem cells before, but I never imagined that their unique abilities could be applied to fully-developed cells too. According to a report from the BBC, that’s exactly what researchers at the Stanford University School of Medicine in California accomplished (you could read the study’s paper in Nature)

The main advantage of stem cells is that they can turn into any other type of specialized cell, proceeding to multiply and function accordingly. Hence their importance in a range of medical treatments in which they could repair damaged tissue or organs (several studies are underway to utilize them in treating strokeheart disease, and some forms of blindness).
 
However, there are some cons as well. Aside from well-known ethical concerns about using embryonic stem cells (the most preferred and effective kind), patients who receive any stem cell tissue would need to take immunosuppressant drugs regularly to prevent their own bodies from attacking it, since it’s biologically foreign. As vast as their benefits may be, there are still many challenges before they could be put to widespread use.
 
For this reason, scientists have been searching for other ways to regenerate loss or damaged tissue.
 
An alternative method has been to take skin cells and reprogram them into “induced” stem cells. These could be made from a patient’s own cells and then turned into the cell type required, however, the process results in cancer-causing genes being activated.
 
The research group, at the Stanford University School of Medicine in California, is looking at another option – converting a person’s own skin cells into specialist cells, without creating “induced” stem cells. It has already transformed skin cells directly into neurons.
 
This study created “neural precursor” cells, which can develop into three types of brain cell: neurons, astrocytes and oligodendrocytes.
 
These precursor cells have the advantage that, once created, they can be grown in a laboratory into very large numbers. This could be critical if the cells were to be used in any therapy.
 
Brain cells and skin cells contain the same genetic information; however, the genetic code is interpreted differently in each. This is controlled by “transcription factors”.
 
The scientists used a virus to infect skin cells with three transcription factors known to be at high levels in neural precursor cells.
 
After three weeks about one in 10 of the cells became neural precursor cells.
 
It’s remarkable to think that our bodies might hold the key to treating a range of afflictions. Imagine suffering from once-irreparable damage to your heart or brain, only to be cured by a few alterations to your own skin sample. I’m sure it’ll be more complex than that, but it’s still a huge advancement, and far beyond what I’d expect us to be capable of.
 
Given that this impressive feat has only been done on mice, it’ll probably be a while until we see any medical application of that sort. It’s not yet known if this replicable in humans, much less if it’s safe and effective. But as always, I’ll be waiting with cautious optimism, marveled by the achievements of human ingenuity.
 

Life Span Increased in Aging Mice

Medicine is continuing to make promising inroads in the area of regenerative medicine. With most developed countries facing increasingly aging populations, there’s widespread concern about mounting healthcare and social security costs.

Furthermore, attention is focusing on ensuring that lives are not only long but also fruitful. Perhaps the greatest hardship of growing old isn’t facing death, but enduring a painful and extended process of physical and mental decline, which furthermore puts an emotional and financial burden on loved ones.
 
Therefore, any practical and ethical means of at least mitigating our inevitable deterioration should be welcomed. The quantity of life means far less without the quality – hence my excitement over a study reported in National Geographic that managed to biologically rejuvenate mice on the verge of death, not only extending their lives but making them function as if they were younger.
 
The study mice were genetically engineered to have a condition similar to a rare human syndrome called progeria, in which children age quickly and die young. (Learn more about the human body.) The fast-aging mice typically die around 21 days after birth, far short of a normal mouse’s two-year life span.
 
When scientists looked at the muscle stem cells of the fast-aging mice, they found what Huard called “tired” stem cells, which don’t divide as quickly.
 
The team then examined mice that had aged normally and found their stem cells were similarly defective.
 
Curious if these deficient stem cells contribute to aging, Huard and colleagues injected stem cells from young, healthy mice into the fast-aging mice about four days before the older animals were expected to die.
 
To Huard’s astonishment, the treated mice lived an average of 71 days—50 more than expected, and the equivalent of an 80-year-old human living to be 200, he said.
 
Not only did the animals live longer, they also seemed healthier, the scientists found.
Despite all the controversy, not to mention the legal and political obstacles (at least here in the US), stem cells continue to yield remarkable results for regenerative medicine, if not medicine as a whole. It is no wonder that many scientists regard stem cell research as one of the most important avenues for improving human health. With more time, money, and societal support, they could have considerable impact on improving the quality of life for millions.
 
Anyway, the implications of this study become more interesting. Like all good scientists, the team undertook repeated experiments to ensure that the first results weren’t fluke, reaching the same outcome in every instance. This raised the vital question as to how the stem cells were having such dramatic effect.
 
To find out, the team “tagged” stem cells injected into the fast-aging mice with a genetic marker that tracked where the cells went inside the body. Surprisingly, the team found only a few stem cells in the mouse organs, squashing a theory that the introduced cells were repairing organ tissues.
 
The scientists went back to the lab to test another idea: that stem cells secrete some kind of mysterious anti-aging substance.
 
The team put stem cells from the fast-aging mice on one side of a flask and stem cells from normal, young mice on the other side. The two sides were separated by a membrane that prevented the cells from touching.
 
Within days, the aging stem cells began acting “younger”—in other words, they began dividing more quickly.
 
“We can conclude that probably normal stem cells secrete something we don’t know that seems to improve the defects in those aging stem cells,” Huard said.
 
“If we can identify that, we have found an anti-aging protein that is going to be important” for people, said Huard, whose study appeared January 3 in the journal Nature Communications.
There is still a lot to learn about stem cells, and it seems we’ve only begun to scratch the surface of their potential benefits. As always, there are important caveats to keep in mind before we get too excited and begin to expect age-reversing medicine on the market.
 
But other scientists are cautious about how soon the discovery may help people delay the aging process or treat age-related disease.
 
“They did a beautiful job of showing that, when they put the muscle stem cells in [the mice], they improved function,” said Justin Lathia, an assistant professor of cell biology at the Cleveland Clinic’s Lerner Research Institute.
 
But as far as people go, it’s still not clear what exactly stem cells do in the body, as well as what the mysterious stem cell secretion really is, Lathia emphasized.
 
Jeremy Rich, chair of the department of Stem Cell Biology and Regenerative Medicine at the Cleveland Clinic, also pointed out that the study is limited to muscle stem cells. That means the research can’t be generalized to include all stem cell types, which are often very different from each other.
 
Paul Frenette, a stem cell and aging expert at the Albert Einstein College of Medicine in New York, called the research “intriguing,” but said one of the messages for “patients is not to get too excited.”
 
“You see all these clinics that are popping up all over the world—even in New York—where they’re injecting stem cells” into people to treat disease, even though such therapies have not been proven.
 
“I don’t think people should run to the clinic right now to have injections of stem cells to live longer.”
Indeed, the news media and general public have a tendency to become overly enthusiastic or supportive of research that is still preliminary or incomplete. In our understandable anticipation of what ground-breaking benefits may emerge, we forget that scientific progress is a cautious, methodical, and arduous journey through a gauntlet of peer review, repeated experimentation, and – in the case of medicine – numerous clinical trials.
 
At the same time, I’ve noticed a pushback against this sentiment from the other direction, in which the response to scientific developments is too cynical or reflexively skeptical. This too is an understandable position, given the sad history of false positives, fraudulence, and exaggerations. It certainly doesn’t help that in age of information overload, we frequently encounter conflicting claims and counter-claims that it can make it difficult for us to make up our minds.
 
Without getting too off topic, I think the key is to maintain a balance between informed incredulity and hope – look at multiple studies, preferably from scientific journals and reputable institutions, and maintain some restraint until more time and scrutiny have passed. I’m obviously very eager about the latency of this finding, but I’m not looking forward to popping anti-aging pills anytime soon.
 
Science isn’t perfect, given human nature, but it has as good a track record as any of our endeavors when it comes to fact-checking. There’s a lot of work to be done.
 
Indeed, study co-author Huard noted that before any human anti-aging trials can begin, scientists need to repeat the experiment in normally aging mice to show whether these mice also live longer.
 
If that turns out to be true, Huard could imagine a scenario in which some of a person’s stem cells are harvested at about age 20 and then injected back into his or her body at around age 50 or 55.
 
Stem cell therapies do already exist for conditions such as incontinence and heart problems, so he thinks “we’re not that far [from applying] this approach clinically down the road.”
 
But Huard warned that such a treatment would not mean a 55-year-old will suddenly look and feel 25 again.
 
“The goal of doing this research is not to [be like a] movie star with a ton of money [who wants to] look great for the rest of their lives,” he said.
 
“The goal is, if you delay aging, maybe you can delay Alzheimer’s or cardiovascular problems.”
 
In other words, he said, such stem cell treatments would help people “age well.”
My thoughts exactly. We’ve made incredible strides in bettering the human condition, doubling or even tripling human life expectancy while – perhaps most crucially – changing the way aging effects people. Older people are becoming unprecedentedly fitter, and it’s no longer unusual to see people running for public office or joining the workforce in their sixties or even early seventies.
 
With the median age in most societies getting higher, even within developing countries, it’s vital to both individual and collective well-being to ensure that the majority of older people can continue to function well into advanced age. The social, economic, and ethical gains would be tremendous.
 

Do Genes Determine Mood?

Studies within the last two or three decades have shed light on the pre-determined factors that make us who we are. Though still hotly debated (and perhaps too often overstated) there is increasing evidence that our personality and behavior are influenced, in varying degrees, by our biology. Alterations to our brain chemistry or hormones, whether deliberately or as the result of certain genes, cause subsequent changes to our mood, cognitive ability, and even morality. As unsettling as it may be for many people, it’s possible that a good part of who we are may be genetically predisposed by the vagaries of biology – a complete accident of birth beyond our control.

The Economist had some time ago published an article on this subject, dealing specifically with the most sought after (and perhaps elusive) of all human emotions: happiness. Feeling good is obviously something any normal person would want, and everyone is concerned with living a good and content life. But figuring out what makes us happy, and how to attain it, has been one of the oldest subjects of debate and literature. With the current economic and political problems that are befalling us, and a growing sense of cynicism and anxiety about the future, concerns about living a stress-free and enjoyable life are understandably widespread.

So imagine the implications of discovering that happiness, if not other emotions, has more to do with your genes than with any existential or spiritual search. Consider the following study detailed below:

[The fact that] personality, along with intelligence, is at least partly heritable is becoming increasingly clear; so, presumably, the tendency to be happy or miserable is, to some extent, passed on through DNA. To try to establish just what that extent is, a group of scientists from University College, London; Harvard Medical School; the University of California, San Diego; and the University of Zurich examined over 1,000 pairs of twins from a huge study on the health of American adolescents. In “Genes, Economics and Happiness”, a working paper from the University of Zurich’s Institute for Empirical Research in Economics, they conclude that about a third of the variation in people’s happiness is heritable.That is along the lines of, though a little lower than, previous estimates on the subject.
 
But while twin studies are useful for establishing the extent to which a characteristic is heritable, they do not finger the particular genes at work. One of the researchers, Jan-Emmanuel De Neve, of University College, London, and the London School of Economics, has tried to do just that, by picking a popular suspect—the gene that encodes the serotonin-transporter protein, a molecule that shuffles a brain messenger called serotonin through cell membranes—and examining how variants of that gene affect levels of happiness.
 
Serotonin is involved in mood regulation. Serotonin transporters are crucial to this job. The serotonin-transporter gene comes in two functional variants—long and short. The long one produces more transporter-protein molecules than the short one. People have two versions (known as alleles) of each gene, one from each parent. So some have two short alleles, some have two long ones, and the rest have one of each.
 
The adolescents in Dr De Neve’s study were asked to grade themselves from very satisfied to very dissatisfied. Dr De Neve found that those with one long allele were 8% more likely than those with none to describe themselves as very satisfied; those with two long alleles were 17% more likely.
 
Correlation doesn’t equal causation, but there still seems to be a strong enough link between these alleles and one’s mood to merit further inspection. Imagine if we could trace other feelings to certain genetic markers as well. Could anger, recklessness, or greed, among other emotions, also be attributed to certain biological factors? What about more severe examples like psychosis? What does all this say about the way we treat certain behavioral or mental problems, both medically and as far as societal attitudes to them?
 
Imagine altering our genetic code in some way could be the key to solving these kinds of problems. Rather than consult a psychotherapist or take some sort of medication, you’d see a specialist in gene therapy instead. Perhaps even mild cases of the blues could be addressed through some sort of genetic tweaking. Granted, I’m getting way ahead of myself here, but it doesn’t hurt to discuss the possibilities, however unlikely they may currently seem.
 
In any case, these scenarios are only the beginning. There is another implication from this study that could be even more contentious:
Where the story could become controversial is when the ethnic origins of the volunteers are taken into account. All were Americans, but they were asked to classify themselves by race as well. On average, the Asian Americans in the sample had 0.69 long genes, the black Americans had 1.47 and the white Americans had 1.12.
 
That result sits comfortably with other studies showing that, on average, Asian countries report lower levels of happiness than their GDP per head would suggest. African countries, however, are all over the place, happiness-wise. But that is not surprising, either. Africa is the most genetically diverse continent, because that is where humanity evolved (Asians, Europeans, Aboriginal Australians and Amerindians are all descended from a few adventurers who left Africa about 60,000 years ago). Black Americans, mostly the descendants of slaves carried away from a few places in West Africa, cannot possibly be representative of the whole continent.
 
That some populations have more of the long version of the serotonin-transporter gene has been noticed before, though the association has previously been made at a national, rather than a racial, level. In a paper in the Proceedings of the Royal Society, published in 2009, Joan Chiao and Katherine Blizinsky of Northwestern University, in Illinois, found a positive correlation between higher levels of the short version of the gene and mood disorders (China and Japan have lots of both) and with collectivist political systems. Their hypothesis is that cultures prone to anxiety tend towards systems that emphasise social harmony and away from ones that emphasise individuals’ independence of each other.
 
Obviously, as with most such findings, more work will have to be done to replicate and validate the conclusions. But the suggestions this discovery makes are vast: not only is everyone’s behavior influenced by genes to a significant level, but so are entire societies and political systems by extension. The way we form our communities, govern ourselves, or go about engaging in economic activity can be informed, in part, by the genetic dispositions of the majority of the population. Does that mean that certain nations, like individuals, are destined for certain paths of development? Such a genetically determined fatalism would be understandably concerning and divisive.
 
As near as we can tell, it would also be an exaggeration. Thus far, most studies have shown that genes, while significant influencers, are not the only determinants of who we are. Being born with a certain genetic predisposition isn’t always destiny. But it’s still something worth keeping in mind. There’s no doubt there will be a lot of debate about this, but there’s one thing that isn’t likely to be disputed:
This latter study may be a few steps too far along the road to genetic determinism for some people. But there is growing interest in the study of happiness, not just among geneticists but also among economists and policymakers dissatisfied with current ways of measuring humanity’s achievements. Future work in this field will be read avidly in those circles.
You can read the actual report of Dr. Neve’s study here. As always, share your thoughts or illuminations below.
 

Genetic Enhancements and Technoprogressive Reflections

In early November, the Transhumanism movement gained another boost when scientists managed to improve the muscle strength of mice by enhancing their genes.

A team of researchers at EPFL, the University of Lausanne and the Salk Institute created super strong, marathon mice and nematodes by reducing the function of a natural inhibitor, suggesting treatments for age-related or genetically caused muscle degeneration are within reach.

It turns out that a tiny inhibitor may be responsible for how strong and powerful our muscles can be. This is the surprising conclusion reached by scientists in EPFL’s Laboratory of Integrative Systems Physiology (LISP), in collaboration with a group in the Center for Integrative Genomics at the University of Lausanne and at the Salk Institute in California. By acting on a receptor (NCoR1), they were able to modulate the transcription of certain genes, creating a strain of mighty mice whose muscles were twice a strong as those of normal mice.

Read the whole article hyperlinked above if you wish to learn more about the technical details of this procedure and the transcription process. Unfortunately, it’s not specified how this process was “modulated,” though I assume it was through the use of some sort of chemical.

At any rate, what I find most interesting is the fact that this was accomplished through a mere* tweaking of a natural genetic component, rather than by a more intrusive or dramatic modification. By my experience, most people imagine gene enhancement to entail a far more drastic process, whereby genes are spliced, mutated, or even synthetically created.

Rather, it seems that many of the more exciting and feasible developments in gene therapy involve a tactical and relatively minimal tweaking of the right genetic parts. It’s more about improving biological efficiency through fine-tuning rather than outright reconstruction. And it seems that this somewhat less radical approach still leads to major results.

In the absence of the inhibitor, the muscle tissue developed much more effectively. The mice with the mutation became true marathoners, capable of running faster and longer before showing any signs of fatigue. In fact, they were able to cover almost twice the distance run by mice that hadn’t received the treatment. They also exhibited better cold tolerance.

Unlike previous experiments with so-called super mice, this study addresses the way energy is burned in the muscle and the way the muscle is built. Examination under a microscope confirmed that the muscle fibers of the modified mice are denser, the muscles are more massive, and the cells in the tissue contain higher numbers of mitochondria–cellular organelles that deliver energy to the muscles.

Only shutting off a specific inhibitor lead to a doubling of muscle strength, which in turn improved stamina, endurance, and even tolerance to colder temperatures (as muscles produce heat). That’s an exponential gain for a rather minor investment, though I wonder how expensive and time consuming the process was.

It was also good that research team followed up on this and closely examined the specific biological effects. As far as I could tell from this and other reports on the experiment, there have been no discernable detrimental effects, and the muscles seem as innately strong and functional as they would be through natural means of improvement.

There’s an even bigger bonus:

Similar results were also observed in nematode worms, allowing the scientists to conclude that their results could be applicable to a large range of living creatures.

This is probably the most important thing to consider, after safety of course. It’s no use improving the bodily function and health of an organism if it’s limited to just lab animals (although they’d probably make for interesting pets on the market). What matters in these kinds of studies is whether the results in question could actually be applicable to humans, which so far seems likely in this case (though it remains to be seen for certain of course).

If we could recreate these results in humans, and do so safely and cheaply, then we’d have the potential to improve the lives of tens of million of people, particularly the elderly, who suffer the most from fatigue or physical weakness due to muscle degeneration (slips and falls alone affect the health of millions of older Americans).

Furthermore, with nearly all populations in the developed world aging quickly, this is a vital way of reducing the subsequently high costs of healthcare and lost productivity, while giving many seniors a new lease on life. Improved functionality would allow people of retirement age to be more productive, participate in the labor force (which many would do if they physically could), and reduce the negative psychological impact of being infirm or feeling burdensome.

But wait, there’s more:

According to a second article published in the same journal and also involving EPFL’s LISP Laboratory, suppressing the NCoR1 receptor in adipose tissues (fat) also led to interesting results. By acting on this corepressor, it was possible to fundamentally change the corpulence of the mice being studied without inducing weight-related diseases. “The specimens that became obese via this treatment did not suffer from diabetes, unlike mice that become obese for other reasons,” notes Auwerx.

The scientists have not yet detected any deleterious side effects associated with eliminating the NCoR1 receptor from muscle and fat tissues, and although the experiments involved genetic manipulations, the researchers are already investigating potential drug molecules that could be used to reduce the receptor’s effectiveness.

So with more investigation, we may derive from this procedure a means of treating diabetes among the millions of mostly obese people that have it. It’s also good that scientists are exploring alternative means of invoking these changes – imagine being able to take a pill or receive a simple shot that improves muscle performance? Though I’m cautious about exaggerating the potential of this until more studies of this recent development are conducted, the long-term therapeutic applications are clearly vast.

As are the potential abuses.

If these results are confirmed in humans, there’s no question it will attract interest from athletes as well as medical experts. “It will be important for anti-doping authorities to monitor that these treatments are not used in an unauthorized manner,” concludes Auwerx.

I’m sure I wasn’t the only one who was drawing an analogy to steroids upon reading this. Imagine the effect on sports across the world, from College Football to the Olympics. How difficult would it be to detect something like a genetic alteration? Would there be any device cheap or efficient enough to do so before every game? What about if there were to be a black market that peddled this stuff to criminals?

Alas, every human achievement, no matter how positive the potential for humanity, is a double-edged sword: nuclear fission, rocketry, and even an improved understanding of chemistry can and have been abused for immoral ends, to name just a few examples. There’s no doubt that something which enhances physical strength will be enticing to dishonest athletes or criminal thugs. We can’t safeguard completely against the vagaries of human nature. But we can plan for it according, and take steps to mitigate abuses. Any research of this nature, especially while it’s still preliminary, should be accompanied with a technoprogressive outlook, which partly entail that the social, political, legal, and ethical implications of any technological or scientific development (especially with transhumanist potential) are taken into consideration.

In this case, researchers must consider the dishonest or illegal ways that this procedure can be utilized. Perhaps they could develop an easy way of detecting alterations to the genetic component, leaving some sort of indicator that is subdued but still noticeable with the right equipment and/or observation. I’ve heard of bioluminescence being used to detect cancerous cells and diseases in the bloodstream – could it somehow work with genetic modifications? Maybe scientists could develop some sort of physical or biological marker, such as something in the bloodstream, or inscribed surgically but minutely in the skin – basically, a genetic ID tag indicating enhancements? I’m just throwing out ideas here.

Meanwhile, policymakers and legal experts should consider sensible regulations over who could manufacture such a muscle enhancer, and/or who could provide the service. We would have to find a balance between limiting the potential for black market production and distribution, and still making it easily accessible for legal and honest intentions. It’s no easy feat, given the precedent of such oversight, but neither would be dealing with widespread illicit abuses.

Then there are the ethical and moral considerations – is it right to alter human beings in this way, even if it were to be beneficial? Are we delving into something that will fundamentally challenge our identities as a species, leading to social or psychological tensions? What if there are indeed detrimental effects that won’t be felt for generations? These are questions that pertain to many transhumanist endeavors.

Arguably, we’re at the cusp of developing all sorts of means to improve the human condition, and must be ready for the wide-ranging outcomes that are not too far off. We can’t predict the future, but we can try our best o prepare for it. Humans should never pursue fundamental changes to our biology or society without proper debate, dialogue, and analysis.

The Berlin Patient and a Possible Cure for HIV/AIDS

A few years ago, at the Charité Medical Universityin Berlin, Germany, a 42-year-old American named Timothy Ray Brown was given an experimental transplant of bone marrow to treat his leukemia, which had failed to respond to first-line chemotherapy. Incidentally, he had also been infected with HIV for more than a decade, for which was taking treatment. The difficult procedure was remarkably successful, but what happened afterward was even more extraordinary, as the Wall Street Journal reports:

The transplant specialists ordered the patient to stop taking his AIDS drugs when they transfused the donor cells, because they feared the powerful drugs might undermine the cells’ ability to survive in their new host. They planned to resume the drugs once HIV re-emerged in the blood.

But it never did. Nearly two years later, standard tests haven’t detected virus in his blood or in the brain and rectal tissues where it often hides.

The man who cured HIV. Will his work lead to a more applicable version?

Almost two years after the transplant, the patient was still recovering from the therapy; but despite reportedly ceasing the taking of antiretroviral medications, HIV remained absent. As of December 2010, three years after the transplant, Brown was still free of any detectable HIV in his blood – he was even indentified in a report posted in the hematological journal, Blood, as effectively “cured”.

Of course, the immediate question on everyone’s mind is: how? HIV is notorious for its incurability, perhaps the most horrific aspect of it. Anti-retrovirals can extend health and longevity by stopping it from replicating and impeding its effects. But they must be taken everyday, are very expensive – especially in the poorer countries that are most ravaged by the disease – and are by no means a sustainable option. Normally when a patient stops taking these treatments, the virus rushes through the body within a few days, or at most a few weeks – any longer than that is unprecedented, especially a full three years.

As it turns out, the blood doctor responsible for the transplant had the search for a cure in mind.

The breakthrough appears to be that Dr. [Gero] Hütter, a soft-spoken hematologist who isn’t an AIDS specialist, deliberately replaced the patient’s bone marrow cells with those from a donor who has a naturally occurring genetic mutation that renders his cells immune to almost all strains of HIV, the virus that causes AIDS.

The mutation in question is an unusual but natural variant of the CCR5 cell-surface receptor, a part of the cell scientists liken to a “door.” This variation had already been known to scientists to make some cells from people born with it resistant to infection with some strains of HIV. But to our knowledge, it had never before been transferrable through a transplant. To understand the significance of this receptor, observe the image and excerpt below:

Back in 1996, when “cocktails” of antiretroviral drugs were proved effective, some researchers proposed that all cells harboring HIV might eventually die off, leading to eradication of HIV from the body — in short, a cure. Those hopes foundered on the discovery that HIV, which integrates itself into a patient’s own DNA, hides in so-called “sanctuary cells,” where it lies dormant yet remains capable of reigniting an infection.

But that same year, researchers discovered that some gay men astonishingly remained uninfected despite engaging in very risky sex with as many as hundreds of partners. These men had inherited a mutation from both their parents that made them virtually immune to HIV.

The mutation prevents a molecule called CCR5 from appearing on the surface of cells. CCR5 acts as a kind of door for the virus. Since most HIV strains must bind to CCR5 to enter cells, the mutation bars the virus from entering. A new AIDS drug, Selzentry, made by Pfizer Inc., doesn’t attack HIV itself but works by blocking CCR5.

About 1% of Europeans, and even more in northern Europe, inherit the CCR5 mutation from both parents. People of African, Asian and South American descent almost never carry it.

Coincidently, most of the countries with the highest rate of infection are in Africa andAsia, where such a mutation is practically nonexistent. But that wouldn’t matter much since very few Europeans, in whom this fascinating trait emerges, seem to have it either. But finding a way to transfer or produce this genetic variation could go a long way to discovering both a preventative measure and a real cure. The prescient German doctor behind this transplant seemed to have that in mind.

Dr. Hütter, 39, remembered this research [with CCR5] when his American leukemia patient failed first-line chemotherapy in 2006. He was treating the patient at Berlin’s Charité Medical University, the same institution where German physician Robert Koch performed some of his groundbreaking research on infectious diseases in the 19th century. Dr. Hütter scoured research on CCR5 and consulted with his superiors.

Finally, he recommended standard second-line treatment: a bone marrow transplant — but from a donor who had inherited the CCR5 mutation from both parents. Bone marrow is where immune-system cells are generated, so transplanting mutant bone-marrow cells would render the patient immune to HIV into perpetuity, at least in theory.

There were a total of 80 compatible blood donors living in Germany. Luckily, on the 61st sample he tested, Dr. Hütter’s colleague Daniel Nowak found one with the mutation from both parents.

To prepare for the transplant, Dr. Hütter first administered a standard regimen of powerful drugs and radiation to kill the patient’s own bone marrow cells and many immune-system cells. This procedure, lethal to many cells that harbor HIV, may have helped the treatment succeed.

Basically, the entire transplant was a complicated – though still ethical – test to replicate HIV immunity. And miraculously, it worked almost immediately. Apparently, a doctor in California had a very eerily similar, though more accidental, experience in 1998. In that instance, a leukemia patient who also had HIV also received a transplant of bone marrow cells, and subsequently had no trace of the disease. Unfortunately, that patient died of the cancer a month and a-half later, and its unknown if the donor cells also had the CCR5 receptor mutation.

The "Berlin Patient:" the first known case of an HIV cure.

Its hard to believe that so little attention has been given to this incredible find, even after all these years. Indeed, though its been covered by numerous major media outlets, few people seem aware of it, and most sources on the subject date from 2008 or 2009.

Of course, a lack of interest could be understandable: HIV has long been established in the popular imagination as an incurable super-illness, and in light of that, many people would probably be initially skeptical of any cure for it. Furthermore, there have been plenty of false-positives before, given the complexity of the HIV virus and its workings.

But even normally incredulous scientists so far seem convinced.

The case was presented to scientists earlier [in 2008] at the Conference on Retroviruses and Opportunistic Infections. In September [of that year], the nonprofit Foundation for AIDS Research, or amFAR, convened a small scientific meeting on the case. Most researchers there believed some HIV still lurks in the patient but that it can’t ignite a raging infection, most likely because its target cells are invulnerable mutants. The scientists agreed that the patient is “functionally cured.”

So far, to my knowledge, no one was raised suspicions or doubts as to the legitimacy of this cure. By early 2011, as reported in New York Magazine, the medical community has come to accept Hütter’s results (New York Magazine has a beautiful and detailed narrative of this cure as well). Of course, as with any potentially ground-breaking discovery, there are numerous caveats to keep in mind, and many more studies will have to be done to confirm the longer-term validity of this cure and whether or not it’s even tenable on a mass scale.

If enough time passes, the extraordinarily protean HIV might evolve to overcome the mutant cells’ invulnerability. Blocking CCR5 might have side effects: A study suggests that people with the mutation are more likely to die from West Nile virus. Most worrisome: The transplant treatment itself, given only to late-stage cancer patients, kills up to 30% of patients. While scientists are drawing up research protocols to try this approach on other leukemia and lymphoma patients, they know it will never be widely used to treat AIDS because of the mortality risk.

…One big hurdle: doctors can’t yet genetically modify all target cells. In theory, HIV would kill off the susceptible ones and, a victim of its own grim success, be left only with the genetically engineered cells that it can’t infect. But so far that’s just theory

Furthermore, as discussed candidly in New Scientist, very few people are compatible donors with the cells that harbor this mutation, making such transplants extremely rare to replicate even a few times, much less on the massive scale required. The same article also noted that HIV sometimes invades white blood cells through an alternative route, the receptor CXCR4.

Of course, this hasn’t stopped researchers and doctors from exploring the implications further and trying to develop alternatives based on what we now know. The most commonly cited venue is gene therapy, which would re-engineer a patient’s own cells to develop the HIV-resistant receptor mutation (or something similar to it). Already, some scientists have formed private companies or undertaken research to better develop this strategy.

We reported on one earlier this year that uses molecular “scissors” called zinc-finger proteins, specifically designed to ruin the CCR5 protein in patients. The approach, developed by a company called Sangamo in San Diego, worked in mice.

Other teams, such as the one led by Nobel-prizewinner David Baltimore at the California Institute of Technology in Pasadena, are developing a similar approach, using molecules called small interfering RNAs (siRNAs) to sabotage production of CCR5 by white blood cells.

Unfortunately, gene therapy carries its own risks and complications. Still in its infancy, there have been some cases where it has failed miserably, often at the cost of a patient’s life. Even some of its successful instances have come at a high price, by costing too much money or causing other serious illnesses to develop in the patient.

Gene therapy is also quite daunting on a technical level. The process currently involves removing cells, modifying them outside the body, and then transfusing them back in – a procedure that is prohibitively expensive and operationally delicate. Even after that threshold is crossed, any therapeutic genes that are developed can so far only be returned using re-engineered viruses as carriers, also known as viral vectors – obviously, they must be made perfectly safe, which is no easy task given the nature of a virus.

Based on my research, most scientists agree that we’re still a long way from improving these methods cheaply and effectively enough to implement on the massive scale required, though we’ve made much advancement over the last few years (including curing a fatal brain disease using, of all things, an HIV vector).

A few of scientists, including Dr. Baltimore, are working on ways of developing carrier viruses of their own that will administer a cure as simply as a flu vaccine does. At the City of Hope Cancer Center inDuarte,California, researchers are even using HIV itself, genetically engineered to be safe, to deliver to a patient’s white blood cells three genes: one that deactivates CCR5, the remainder to disable HIV. The procedure has already been performed on a few patients, though I’ve yet to find any updates on it.

For me, the greatest obstacle of all, which wasn’t mentioned in the sources I consulted, is one of compassion: even if we developed a working, mass-producible cure, administering it to the millions of mostly impoverished people who are infected is a whole different challenge altogether. After all, we’ve long had cures for such virulent diseases as tuberculosis, malaria, and others, yet millions of people continue to die of these diseases every year.

So aside, from technological and medical challenges, there are social, political, economic, and ethical factors that must be addressed for the cure to have any meaning – and these things are arguably more complex and difficult to solve.

One thing that is clear is that we’re a lot closer to a cure than ever before, and if history is any indicator, we’ll continue with exponential developments for years to come (so long as ample research funding is continued that is). It would be amazing to think that, within my lifetime, it’s probable that this horrible affliction will join dozens of other diseases in being extinguished into the annals of history.

Signs of Aging Stopped in Mice

Scientists in the Mayo Clinic have managed to reduce or even completely eliminate the pathology of aging, including wrinkles, cataracts, and muscle atrophy. From the BBC article:

Scientists at the Mayo Clinic, in the US, devised a way to kill all senescent cells in genetically engineered mice.

The animals would age far more quickly than normal, and when they were given a drug, the senescent cells would die.

The researchers looked at three symptoms of old age: formation of cataracts in the eye; the wasting away of muscle tissue; and the loss of fat deposits under the skin, which keep it smooth.

Researchers said the onset of these symptoms was “dramatically delayed” when the animals were treated with the drug.

When it was given after the mice had been allowed to age, there was an improvement in muscle function.

One of the researchers, Dr James Kirkland, said: “I’ve never seen anything quite like it.”

His colleague Dr Jan van Deursen told the BBC: “We were very surprised by the very profound effect. I really think this is very significant.”

The treatment had no effect on lifespan, but that may be due to the type of genetically engineered mouse used.

Senescent cells are those which have stopped dividing. While they help prevent tumors from progressing, and often get cleared out by the immune system, they inevitably build up overtime, contributing to the symptoms of aging. Removing these cells doesn’t stop the actual biological process of aging itself – this isn’t the key to immortality – but they do improve the quality of life at old age, and that is arguably just as important.

This study brings us closer to figuring out the other side of the coin when it comes to increasing longevity – living a long life is one thing, but ensuring that life is worth living in the first place is a whole other matter. Suffering from all manner of debilitating effects – senility, muscle weakness, impaired senses – can make the advantages of a longer lifespan on this Earth moot.

Of course, like good scientists, the researchers are cautioning that this shouldn’t be taken as a done deal. The experiment was just a preliminary one, and was done only with mice – we’re not yet able to simply purge these senescent cells from our own bodies.

But it opens up the prospect of doing so, or at least helping the process along. We can try to devise a drug that stops these cells directly for example. One of the scientists involved noted that younger people are already at the point that their immune systems mostly clean these “aging” cells out – so boosting or priming immunity in some way may preempt the effects of growing old, changing forever the way we view aging or how we define “being old” (which is already being shifted through advances in nutrition and medicine).

Very exciting prospects indeed. If anyone else is interested, check out the original published work in Nature.

 

 

Gregor Mendel

Last Wednesday, July 20th, was the 189th birthday of Gregor Mendel, an Austrian scientist and monk who was posthumously recognized as the the founder of genetics. Google thoughtfully honored his vast contribution to this accomplishment through a clever doodle that was  likely noticed by millions – though I don’t know how many bothered to investigate it further.

In any case, it’s great to see some well-deserved attention directed at these often underrated or forgotten figures of history. I had the fortune of learning about Mendel and his experiments back in grade school, and have remembered him ever since then. I remember being amazed – as I still am – at how a humble monk growing  some peas could inadvertently stumble upon a “modern” scientific field like genetics (which many of us, myself included, usually assume to be the sort of thing we could’ve only discover recently, with modern technology).

Genetics is probably one of the most important and rapidly progressing scientific field in our time, with vast implications for our survival – everything from growing durable and more high yielding crops to curing, or preemptively wiping out, numerous diseases. What’s most fascinating is that Mendel himself and his contemporaries didn’t realize the great significance of his discovery that organisms inherited certain traits in an organized, structured way; it wasn’t until decades later, long after his death, that this work was independently rediscovered and his role in the matter recognized (the genetic laws he discovered were indeed named after him).

I also find it interesting that Mendel was a Catholic monk (an Augustinian friar to be precise). Sure enough, the man that developed the famous Big Bang theory, Lemaitre, was a Catholic priest – as surprising as it is ironic I’m sure. Many people, particularly on the political left, tend to prescribe to the erroneous “conflict thesis” that holds that there is a systemic and historical conflict between religion and science. Granted, to a certain degree this was true, and remains so to this day, such as with evolution (which most of the major church’s do officially recognize, to their credit) and with scientific discoveries that confirm a biological origin to homosexuality.

But for the most part, religion in itself was nowhere near as oppressive to scientific progress as is commonly believed, and there are a number of prominent religious and even clerical scientists that attest to this. Indeed, monks and other religious ascetics like Mendel were generally quite astute when it came to achievements in science, medicine, naturalism, and even cuisine. Their isolation from urban settlements allowed them to explore the vast expanse of nature surrounding their monestaries, from which they subsequently discovered many new plants, animals, and medicinal herbs. Their simple living – shed of busying responsibilities to a job or supporting a family – freed up plenty of time and concentration to contemplate new ideas and philosophies, and to experiment in the same way as our proto-geneticist did.

Even their faith, often seen as a detriment to science, contributed in its own way – because they believed the universe to have been God’s creation, it was up to them, as his greatest creations, to explore and understand their creator’s grand design. This religious philosophy contributed to the curiosity and wonder that we recognize as a necessary prerequisite to science. Unfortunately, it isn’t always applied in a high-minded and constructive way: a cure for small-pox, for example, was long frustrated by some theologians and religious authorities that believed it to be the work of God, not of medicine. And the application of dogmatic and puritanical strains of religious thought has to this day kept significant segments of society in the dark, including ideologically (i.e. close-mindedness, lack of exposure to other faiths, deferring to authority rather than empiricism, etc).

But even an irreligious individual with a critical outlook on religion and the supernatural could give credit where it’s due, not that I’m trying to paint an entirely rosy picture on the science-faith debate (which I’d like to address in a whole other post). Ultimately, regardless of his religious or ideological background, Mendel succeeded in his crucial work because of one powerful universal human ability: curiosity. As long as we maintain a sense of wonder and inquisitiveness about the world around us, tap into it, and most importantly apply it, we’ll always continue to progress in a manner that hopefully transcends our differences – assuming keep an openness to reason, illumination, and freethinking.