The English word “person” has a long and convoluted history. Though the word itself likely derives from the Latin, persona, referring to the masks worn in theatre, its meaning has evolved over time. One of the biggest conceptual overhauls came in the 4th century AD during a church council that was held to investigate the concept…
It’s difficult to overstate our society’s fascination with Artificial Intelligence (AI). From the millions of people who tuned in every week for the new HBO show WestWorld to home assistants like Amazon’s Echo and Google Home, Americans fully embrace the notion of “smart machines.” As a peculiar apex of our ability to craft tools, smart…
Though we often take for granted that humans are persons, they are not exempt from questions surrounding personhood. Indeed, what it means to be a person is largely an unsettled argument, even though we often speak of “people” and “persons.” Just as it’s important to ask if other beings might ever be persons, it is […]
Last week, 20 months of negotiations between 7 different countries came to fruition. The Joint Comprehensive Plan of Action (JCPOA) was signed by the US, China, Russia, UK, France, Germany, and Iran. The Iran Nuclear Deal, as it has been popularized, is a groundbreaking event in diplomacy with one of the most volatile nations in an area of the world that is historically unstable. The JCPOA has many confused about not only the details, but also the general concepts of the plan. I will try to keep jargon low and explained, so that this post will, hopefully, dispel some of the confusion.
Here are some terms for those unfamiliar with the uranium enrichment process:
Isotope – A variant of an element that has a particular mass (number of neutrons + protons). Heavier and odd numbered isotopes tend to be less stable.
Uranium 235 – The uranium isotope that is easily split (fissile) to produce energy. Uranium ore contains 0.7% U-235.
Uranium 238 – A stable uranium isotope that is not fissile and is not used for energy. Uranium ore contains 99.3% U-238.
Plutonium 239 – A fissile byproduct of nuclear reactors
Heavy Water – Water molecules that contain Deuterium, which is a stable isotope of Hydrogen containing an extra neutron, giving it greater mass.
Low Enriched Uranium – Uranium with less than 20% concentration of U-235.
Highly enriched Uranium – Uranium with greater than 20% concentration of U-235.
Uranium Hexafluoride (UF6) – Uranium that is bound to 6 fluorides. This form of Uranium is necessary for enrichment with the gas centrifuges.
Uranium Dioxide – Uranium bonded with two Oxygens. This form of Uranium is packed into fuel rods and used as fuel for nuclear reactors.
Beta decay – A neutron can be seen as a proton and an electron combined. During beta decay, the neutron emits the electron (referred to as a beta particle, hence beta decay), which effectively turns the neutron into a proton, thus changing the element into a new element (one that is immediately after it on the periodic table). For example, if Carbon (#6 on the table) beta decayed, it would become Nitrogen (#7). This occurs in the atmosphere as a part of the Carbon 14 cycle.
The most common thing I’ve heard regarding the deal is that people are uncomfortable with the Iran having nuclear power “now.” This, I assume, stems from a misunderstanding of what the deal was designed to do. The JCPOA doesn’t give Iran anything; Iran has had a nuclear program for years, and has been enriching uranium to amounts that are pushing the boundaries of normal energy usage. The JCPOA will require Iran to do a few things to reduce the chances of them creating a nuclear weapon, which I will explain one by one:
- Reduce their current uranium stockpile by about 96%
- No Uranium enrichment beyond 3.67% for 15 years
- Use only ~ 5000 of the lowest efficiency centrifuges (out of about 19,000) for the next 10 years.
- Redesign the Arak heavy water reactor
- No building heavy water reactors or stockpiling of heavy water for 15 years
- Allow comprehensive and unprecedented international inspections of facilities by the International Atomic Energy Agency (IAEA)
- Convert the underground Fordow nuclear facility into a nuclear, physics, and technology center where international scientists will also be stationed
- Ship spent fuel to other countries
- In return for the above tenets being met, economically crippling sanctions by the UN, EU, US, and possibly other individual countries, will be lifted.
Let’s start with the first – Stockpile reduction:
This one seems to be an obvious win. Iran has around 20,000 lbs of low enriched uranium (~5% U-235) stockpiled. With this provision in place, they would be reduced to 660 lbs of low enriched uranium on hand. The reduction would be done by either shipping the uranium out of the country or diluting it. Iran also held about 460 lbs of 20% enriched Uranium. Since January, 238.5 lbs of this has been diluted to less than 5% enrichment. A little over a pound was retained by the IAEA for reference, a fraction of a pound was taken by the IAEA for sampling, and the remaining 220 lbs is in the process of being converted into Uranium dioxide, which is used for fuel rods. Research reactors, like the one what Tehran, run on fuel rods with 20% enriched uranium. Iran’s Fuel Plate Fabrication Plant has no process line by which the oxide can be converted back to UF6 to be further enriched.
3.67% enrichment cap:
The percentage of U-235 (enrichment level) in your Uranium says a lot about your intentions. Uranium that is enriched to 3-5% is used in regular nuclear reactors for energy production. Uranium at 20% enrichment is often used for research and production of medical isotopes. Iran claims that it has enriched uranium to 20% in order to supply the Tehran reactor for production of medical isotopes. This is actually not an unreasonable claim. The last shipment of 20% uranium into the country was in 1992 by Argentina. This would last about 20 years at the most, so Iran does need 20% enriched uranium to continue production of medical isotopes that are used in everything from radiation treatment to medical imaging.
Cut in centrifuge use:
The details on the types of centrifuges and their usage are some of the more complex parts of the JCPOA. However, the main points are pretty straightforward. The gas centrifuges used to enrich uranium are a little different than the typical scientific centrifuge. These centrifuges use diffusion of gaseous UF6 (see terms above) to separate the lighter U-235 from the heavier U-238. This process isn’t too efficient, particularly with the old equipment that Iran would be required to use. Successful enrichment, even to 3.67%, requires an assembly line of centrifuges, where the products of one centrifuge becomes the reactants of another. Keep in mind that uranium ore contains less than 1% U-235. Under the JCPOA, Iran would only be allowed to use about 6000 of their almost 20,000 centrifuges. Is this enough to make a bomb? Sure. I suppose 600 would be enough. However, the point is to make is difficult – and overt – for Iran to enrich uranium to weapons grade.
Redesigning the Arak Heavy Water Reactor:
The details on this are vague as of now. Supposedly, the reactor core will be filled with concrete and then redesigned according to UN regulations with the help of international scientists. Claims are that this will help reduce the potential of Plutonium being produced in high quantities. I’m not entirely sure what kind of redesign would significantly reduce this potential, other than the fact that heavy water reactors do not require enriched uranium. Because the water is “heavy,” the reaction process is much more efficient. Heavy water already has extra neutrons, and so it is less likely to absorb the neutrons that are used to split U-235. Thus, your concentration of U-235 doesn’t need to be as high to achieve efficiency. A consequence of low-concentration U-235 is over 99% concentration of U-238. U-238 doesn’t split easily, so it tends to absorb neutrons, which will be in even higher abundance if the water isn’t absorbing them. When U-238 absorbs a neutron, it becomes U-239, which is unstable and beta decays (see terms for info) into Neptunium 239. Neptunium 239 is also unstable, so it beta decays into Plutonium 239, which can be used as fuel in the same way as U-235 if left in the fuel rod. However, Plutonium 239 can be removed as it is created and replaced with more Uranium. This is how Weapons grade Plutonium is stockpiled. Fortunately, this shouldn’t be a difficult thing for IAEA to monitor, as the inspectors will know how much should be present. Much of the success of this deal will fall on how well the inspectors do their jobs.
No stockpiling heavy water or building heavy water reactors for 15 years:
This follows the previous point. Not only will Arak be redesigned, but Iran will not be allowed to build or collect material (heavy water) to build a heavy water reactor for 15 years.
This part of the deal is a bit vague as well. However, it is one of the most important aspects. Iran is essentially on probation right now, and the IAEA is its probation officer. If Iran does anything wrong, sanctions, the levying of which are the main reason Iran is trying to make a deal, will immediately go into effect. It would be counterintuitive for them to break the rules overtly, and should be relatively easy to catch if they try to do so covertly. IAEA inspectors will have the ability to inspect not only current reactors and research (not to mention the monitoring or uranium mining and import), but will also be able to inspect “suspicious” areas. There is an appeals committee, and it could take up to a maximum of 4 weeks if Iran claims the inspection unnecessary. However, let’s be real. The US and the rest of the world’s intelligence will be all over any suspicions of the IAEA inspectors. If it’s happening, especially on any scale that could be dangerous, we will find out. The last thing Iran wants is to be resanctioned and show that it cannot be trusted under any circumstances. Even a bad kid does what’s in his or her best interest.
Converting Fordow into a research center:
Fordow is a heavily fortified, underground nuclear reactor. Under the JCPOA, Iran will not enrich any Uranium at Fordow, will convert it to a research center, and will allow international scientists to be stationed there. So, not only will IAEA have inspection capabilities, but the world will have scientific eyes inside of this facility, further reducing any chances of covert, illegitimate activity.
Shipping off spent fuel:
Spent fuel rods are where you get Plutonium 239, as described previously. Under the JCPOA, Iran will ship spent fuel rods out of the country for the lifetime of the Arak reactor, and will not build a reprocessing facility (necessary to separate out plutonium) for 15 years.
Sanctions will be lifted:
Economic sanctions from the US, EU, and UN, as well as other independent countries, has crippled Iran’s economy. These sanctions include heavily restricted imports and exports on many things, including oil, which is one of Iran’s biggest exports. Additionally, Iran has over $100 billion in frozen assets overseas, and was banned from participating in the international banking system. The economic sanctions crippled Iran for many years, deteriorating the quality of life for citizens as collateral damage. The sanctions will be lifted as Iran continues to show cooperation, allowing Iran to prove to the rest of the world that is can be a legitimate part of world trade.
Iran has been in “prison” the last decade or so. They have been showing good behavior through diluting uranium stockpiles even before last weeks agreement was reached. They are now essentially on probation for 15 years. This can be analogous to a recently released prisoner. You don’t just set them free; they do their time and then you assign them a probation officer – in this case it’s the IAEA. If the person shows good behavior and a willingness to be a contributing member of society, they will be allowed more freedom. This is where Iran is at with the JCPOA. This is why it’s a 15 year deal. Iran has 15 years to prove to the world that they can be a participating country in global interactions. The world will have 15 years to learn about Iran’s capabilities and prepare in the event that they break their probation. But, just as a prisoner wants nothing more than to avoid going back to prison, Iran wants nothing more than to avoid sanctions. This deal gives us a chance to form a somewhat diplomatic relationship with a country that, in the past, has been difficult to negotiate with. ISIS is also one of Iran’s biggest enemies, and this diplomatic relationship might help curtail them, but that is a topic for another post. Will this fix all the problems in the Middle East? No. Is Iran our ally now? Absolutely not. Ultimately, this deal lowers the chance of Iran creating a nuclear bomb, gives them a chance to demonstrate their ability to cooperate and participate in global affairs, and is a step closer to stabilizing the Middle East.
For those of you who are still wanting to use military action against Iran (because the West’s military interventions in the Middle East have been SO successful in the past) instead of trying diplomacy first, please read the document in the link below. It is an assessment of the pros and cons of military intervention in Iran by one of the most well regarded and respected think tank organizations in the world.
Empirically testing health-related hypotheses formulated through an evolutionary lens can prove to be difficult. The environment and the human experience are radically different from the first 6 million years of human evolution. Living on the edge of human existence and the top end of the techno-scientific scale, we are far removed from the environment to which many of our genes are hypothesized to be properly suited. Fortunately, the human race is a diverse group of individuals who have dispersed across the globe and have acclimated to a variety of circumstances. Accordingly, a few hunter-gatherer societies remain in parts of Africa. Though neither their genes nor their cultures are identical to original hunter-gatherers, they do retain the closest genetic and sociocultural similarity to human ancestors in the modern world. This is not to say that they are “less evolved” than other human societies. This notion is elementary and indicative of evolutionary ignorance. They are very well suited for their habitat, both genetically and culturally. Fortunately, those of us who are less suited for our environments, both genetically and culturally (i.e., everyone else, particularly in the US), can glean incredible insights about the functioning our own bodies and to what dietary and daily circumstances our physiology is best suited.
I recently wrote a primer on evolutionary medicine (which can be found here), which might be beneficial to read before getting into the specifics. This post will focus on myopia, or “near-sightedness,” the visual condition where objects at a distance are out of focus. Myopia affects about 15% of Africans, a third of Americans and Europeans, and over 75% of Asians – a curious bias that I’ll address later in the article. Fortunately (sort-of), myopia is easy to treat with glasses or contacts, and can even be cured to some extent with Laser-Assisted in situ Keratomileusis, commonly known as LASIK. Myopia occurs when the eye is too long, causing the focal point of light to occur prematurely, resulting in a blurry image. As a result, corrective lenses refract the light before it hits the cornea, essentially “overshooting” the refraction. For example, myopic corrective lenses will be thicker on the sides and thinner in the middle, causing the light to spread out slightly more before it hits the cornea, ultimately moving the focal point further back in the eyeball. With LASIK, a high frequency laser is used to vaporize (note: no heat is used. The vaporization is due to the light wavelength) tissue on the center of the cornea, thus reshaping the cornea so that light will be correctly refracted.
In order to focus, the eye depends on ciliary muscles that are attached to the lens. When focusing on something far away, as would often be the case outdoors, the ciliary muscles contract, stretching the lens to a flattened shape. When focusing on something up close, such as a book, television, computer, or phone, the muscles relax, allowing the lens to become more concave. Think of a camera lens: to focus on something far away, you use a longer lens or zoom in. Doing this moves the focal point of distant objects further back, allowing them to be in focus. To take up-close shots you use a macro lens, which is a very short, rounded lens that moves the focal point for near objects closer to the lens. This is how the eye works. Myopia is what happens when your zoom function is broken. Evolution and an analysis of our current sociocultural context might be able to tell us why this happens.
I’m a student, and spend a lot of my time looking at a book, a laptop, or a phone. I love to get outside when I can, but, ultimately, most of my time is spent looking at things up-close. That means that the ciliary muscles in my eye – the zoom muscles – spend most of their time relaxed. Just like any other muscle that goes unused, the ciliary muscle will likely begin to atrophy and become weaker (as far as I’m aware, no quantitative studies have been performed on ciliary muscle size or mitochondrial count, probably because this would be difficult or impossible to do on a living person. Perhaps future studies can examine the ciliary muscles of recently deceased individuals and compare individuals who suffered from myopia with individuals who had normal vision). Over time, particularly if it occurs throughout critical stages of development during childhood, the muscles may become to weak to contract and properly pull the lens flat, thus preventing you from being able to focus on distant objects. Of course, this begs the question of whether or not the muscle be strengthened. I don’t know, and I’m not sure that I am willing to find out by using myself as a guinea pig. Unfortunately, that makes me part of the problem of “dysevolution,” as coined by Harvard paleoanthropologist and human evolutionary biologist, Daniel Lieberman. Dysevolution refers to the circle of treating diseases without trying to change or fix the cause. Our technology and scientific understanding has advanced so rapidly in the past 100 years that we can fix things such as myopia with ease. Often this cycle is perpetuated by comfort. Why change what the way I do things when I can just buy contacts or glasses? My previous post mentions several other possible mismatch diseases, and Lieberman’s book, “The Story of the Human Body,” goes into detail about many of them. For many of them – if not most – we simply ignore the possible cures and instead opt for a more “comfortable” and easy treatment. However, this cycle is sure to grow and intensify as time goes on.
Evolutionary medicine is sometimes difficult to empirically test. However, as mentioned above, modern day hunter-gatherer societies can offer incredible insight and points of comparison for how sociocultural differences may affect our “mismatch diseases.” Studies of this kind are unfortunately few and far between (possibly because research funding also focuses on treatments). However, studies with hunter-gatherer societies have shown that very few members suffer from myopia (as well as many other non-infectious ailments, such as type-2 diabetes, heart disease, osteoporosis, and even cavities). The thought is that they are exposed to a variety of visual stimuli and their visual environment is constantly changing. This “exercises” their ciliary muscles and keeps them strong. Experiments have also shown that animals that are deprived of visual stimuli will grow elongated eyeballs. Similarly, people who spend more time indoors, particularly with studying, as is common in many Asian cultures, exhibit much higher instances of myopia whereas those who spend some time outdoors, as is more common in many African cultures, tend to have a lower rate of myopia. Our eyes did not evolve to see things 2 feet from our face all day long. They evolved to keep up alive from the plethora of visual stimuli in nature and to help us search for food: 2 things that many people, particularly children in developed countries, no longer need to do.
The solution isn’t to give up studying and electronics. It’s much more simple than that. Nearly everyone uses books and electronics, so why doesn’t everyone have myopia? One possibility is genetics, though that doesn’t seem like a plausible explanation. Rates of myopia have only skyrocketed in the last century, and any latent mutation for poor vision would have most certainly been selected against in our ancestors. The likely “cure” for myopia is balance. Spend time outside, especially as a child. The data from lab experiments as well as social statistics seem to point in this direction. If we continue to ignore the cause and only treat the symptoms, we are trapping ourselves in an ever growing cycle in which we become more and more dependent upon technology.
Humans have evolved a most unique mastery of toolmaking through advanced technology. As an extension of our biological bodies, technology has loosened the grip of natural selection. This is particularly true in the field of biomedicine and genetic engineering. We have the ability to directly alter the blueprint of life for any purpose we wish. Beginning in the 1970’s with the creation of recombinant DNA and transgenic organisms, genetic engineering has offered scientists the ability to study genes on a level that may not have seemed possible at the time. The field has provided a wealth of knowledge as well as practical implications, such as knockout mice and the ability to produce near-endless amount of human insulin for diabetics.
As of 2009, multiplex automated genome engineering (MAGE) has ushered in a new branch of genetic engineering – genomic engineering. We are no longer restricted to altering single genes, but rather are able to alter entire genomes by manipulating several genes in parallel. This new ability, brought about by MAGE technology, allows for nearly endless applications that stretch well beyond medicine or industry; agriculture, evolutionary biology, and conservation biology will benefit tremendously as MAGE technology progresses. Genetic engineering advancements such as MAGE are poised to revolutionize entire fields of science, including synthetic biology, molecular biology, and genetics by offering faster, cheaper, and more powerful methods of genome engineering.
Genetic engineering underwent a revolutionary change in the 1980’s, largely due to the pioneering work of Martin Evans, Mario Capecchi, and Oliver Smithies. Evans and Kauffman were the first to describe a method for extracting, isolating, and culturing mouse embryonic stem cells. This laid the foundation for gene targeting, a method that was independently discovered by both Oliver Smithies and Mario Capecchi. Mario Capecchi and his colleagues were the first to suggest mammalian cells had the machinery capable for homologous recombination with exogenous DNA. Smithies took this a step further, demonstrating targeted gene insertion using the β-globin gene. Ultimately, the combined work of Evans, Smithies, and Capecchi on homologous recombination earned them the Nobel Prize in Physiology or Medicine in 2007. The science of homologous recombination has allowed for many scientific discoveries, primarily through the creation of knockout mice.
Homologous recombination works under many of the same principles are chromosomal recombination in meiosis, wherein homologous genetic sequences are randomly exchanged. The difference lies in the fact that homologous recombination works with exogenous DNA and on a gene level rather than chromosomal level.
The method works by using a double stranded genetic construct with flanking regions that are homologous to the flanking regions of the gene of interest. This allows for the sequence in the middle, containing a positive selection marker and new gene, to be incorporated. The positive control should be something that can be selected for, such as resistance to a toxin or a color change. Outside of one of the flanking regions of the construct should lie a negative selection marker; the thymidine kinase gene is commonly used. If homologous recombination is too lenient, and the thymidine kinase gene is incorporated into the endogenous DNA, it can be detected and disposed of. This is to prevent too much genetic information from being exchanged.
Using this method, knockout mice can be created. A knockout mouse is a mouse that is lacking a functional gene, allowing for elucidation of the gene’s function. Embryonic stem cells are extracted from a mouse blastocyst and introduced to the gene construct via electroporation. The successfully genetically modified stem cells are selected using the positive and negative markers. These are isolated and cultured before being inserted back into mouse blastocysts. The mouse blastocysts can then be inserted into female mice, producing chimeric offspring. These offspring may be mated to wild-type mice. If the germ cells of the chimeric mouse were generated from the modified stem cells, then the offspring will be heterozygous for the modified gene and wild-type gene. These heterozygous mice can then be interbred, with a portion of the offspring being homozygous for the modified gene. This is the beginning of a mouse line with the chosen gene “knocked-out.”
Multiplex Automated Genome Engineering Process
The major drawback of the previously described method of “gene targeting” is the inability to multiplex. The process is not very efficient, and targeting more than one gene becomes problematic, limiting homologous recombination to single genes. In 2009, George Church and colleagues solved this issue with the creation of multiplex automated genome engineering (MAGE). MAGE technology uses hybridizing oligonucleotides to alter multiple genes in parallel. The machine may be thought of as an “evolution machine,” wherein favorable sequences are chosen at a higher frequency than less favorable sequences. The hybridization free energy is a predictor of allelic replacement efficiency. As cycles complete, sequences become more similar to the oligonucleotide sequence, increasing the chance that those sequences will be further altered by hybridization. Eventually, the majority of endogenous sequences will be completely replaced with the sequence of the oligonucleotide. This process only takes about 6-8 cycles.
After the E. coli cells are grown to the mid log phase, expression of the beta protein is induced. Cells are chilled and the media is drained. A solution containing the oligonucleotides is added, followed by electroporation. This step is particularly lethal, killing many of the cells. However, the cells are chosen based on positive markers (optional, but increases efficiency) and allowed to reach the mid-log phase again before repeating the process. Church and his colleagues have optimized the E. coli strain EcNR2 to work with MAGE. EcNR2 contains a plasmid with the λ phage genes exo, beta, and gam as well as being mismatch gene deficient. When expressed, the phage genes will help keep the oligonucleotide annealed to the lagging strand of the DNA during replication, while the mismatch gene deficiency prevents the cellular repair mechanisms from changing the oligonucleotide sequence once it is annealed. Using an improved technique called co-selection MAGE (CoS-MAGE), Church and colleagues created EcHW47, the successor to EcNR2. In CoS-MAGE, cells that exhibit naturally superior oligo-uptake are selected for before attempting to target the genes of interest.
MAGE technology is currently in the process of being refined, but shows incredible promise in practical applications. Some of the immediate applications include the ability to more easily and directly study molecular evolution and the creation of more efficient bacterial production of industrial chemicals and biologically relevant hormones. Once the technique has been optimized in plants and mammals, immediate applications could be realized in GMO production and creation of multi-knockout mice that will give scientists the ability to study gene-gene interactions on a level previously unattainable. A more optimistic and perhaps grandiose vision could see MAGE working towards ending genetic disorders (CRISPR technology, an equally incredible genomic editing technique, may beat MAGE there) and serving as a cornerstone technique in de-extinction. The ability to alter a genome in any fashion brings with it immense power. The possibilities for MAGE are boundless, unimaginable, and are sure to change genomic science.
For more information on Homologous recombination, see:
For more information on MAGE, see:
Wang, H. H., Isaacs, F. J., Carr, P. A., Sun, Z. Z., Xu, G., Forest, C. R., & Church, G. M. (2009). Programming cells by multiplex genome engineering and accelerated evolution. Nature, 460(7257), 894-898.
Wang, H. H., Kim, H., Cong, L., Jeong, J., Bang, D., & Church, G. M. (2012). Genome-scale promoter engineering by coselection MAGE. Nature methods, 9(6), 591-593.
For more information on CRISPR (which I highly recommend; it’s fascinating), see: