Author Archives: theusernamewhichismine

What was the best 10-year period to invest in the S&P 500?

I’m doing a small project right now looking at whether stop losses are actually useful in investing. When FTX blew up, it was noted that the traders there didn’t believe in stop losses, for which they were ridiculed on social media. Of course, do stop losses actually help? Or are they more likely to kick you out of a volatile-but-profitable investment than save you from an unprofitable one? Well I can’t answer that yet, but I can answer a different question.

To start my project, I downloaded 30ish years of S&P 500 data starting September 1990 and asked a quick question: what 10-year period gave the best return if you had invested in the S&P? Once I get the baseline return down, I can add in things like stop-losses and momentum strategies to see if a savvy investor could have improved their return with simple rules. Anyway, here’s the data:

I make a small program to estimate the return if you have bought $10,000 of S&P 500 stocks and simply held them for 10 years, selling them at the end of the 10th year. From this we can see that 1990 would have by far been the best years to start as you would have been able to sell at the peak of the Dotcom Bubble. Just a couple of years later however and you would have sold into the Dotcom Crash instead, drastically lowering your returns. The worst years for a 10-year buy-and-hold were 1998-2000 as you would have sold into the teeth of the Financial Crisis. These are only years where your 10-year return would have been negative. Then we can see 2008-2009 themselves as some of the best years to start investing, since you would have bought right at the bottom and ridden strong returns into 2018-2019.

I hope to update the program soon to see if momentum strategies beat buy-and-hold, but for now this gives a good picture of the historical returns for the S&P 500. The average 10-year-return was 100%, but with an 80% standard deviation. The absolute worst return would have been to start investing March 30th 1999, you would have bought into the Dotcom Bubble and sold into the Financial Crisis with a net return of -48%. The best 10-year-return was to start October 11, 1990, which would have had you buy very low and sell near the tippy top of the Dotcom Bubble for a 510% return. There are some wild swings with the buy-and-hold strategy, but the average is still very positive, we’ll see later if stop-losses can beat that.

Send troops to the Fed?

Pardon me for wading into Twitter Drama, but Rohan Grey is a remarkably unserious “intellectual” and I couldn’t help myself.

Before I start, let me share a tiny story from “Zen and the Art of Motorcycle Maintenance.” This book was a thoroughly unenjoyable read for teenaged me, but it has one anecdote that still sticks with me. If memory serves, there is a university that is being threatened with losing its accreditation due to repeated failures and the students are naturally protesting as this would make their degrees worthless. One student talks to the narrator and claims that the University in fact can’t lose its accreditation, because if someone tried to take it “the Governor would send the national guard to protect us!”

I shouldn’t have to spell out the ridiculousness, but I want to hit word count so I will. Accreditation isn’t held in a vault, it isn’t something you can protect with guns and soldiers. Accreditation is the trust that other institutions have in you, and while some of it is legally codified most of its power is in the uncodified trust that a society is built on. You can’t protect accreditation with and soldiers any more than you can protect trust or friendship.

And so it was with bewilderment that I read an Assistant Law Professor on Twitter making the same mistakes as the nameless student from a book. Rohan Grey wants to do an end-run around the debt ceiling by having the Treasury mint a one trillion dollar platinum coin and deposit it in the Federal Reserve. This coin would then pay for the USA’s financial obligations without the need to borrow money. A big (and usually ignored) problem is that the Fed would have to accept the coin, and as Josh Barro writes, the Fed has expressed the opinion that this chicanery is illegal and undermines Fed independence. (Read Barro’s article, it goes into great detail as to why this idea probably wouldn’t work). Undeterred, Grey thinks the Fed’s opinion doesn’t matter, and that if they refuse to accept the coin then Biden should send troops to the Federal Reserve and force them to accept it.

Grey’s mistake is thinking that guns can be used to enforce trust. The Federal Reserve has the trust of the markets, and its power to move markets is based on that trust as much as anything else. The Federal Reserve trades bonds and sets rates, but those bonds and rates have value because people trust the Fed to keep its word, Jerome Powell’s speeches about the Fed’s plans have as much or more power as any action taken by the Fed. Now imagine a scenario where troops are instructed to besiege and occupy the Federal Reserve, where Powell is held at gunpoint and forced to accept a one trillion dollar deposit from the Treasury which he and the Fed have gone on record as saying is illegal. Trust in the Fed would be shattered, nothing Powell says or does matters anymore because the troops (and by extension the President) are running the show. Investors would flee from US government bonds, causing yields (and thus America’s cost of borrowing) to skyrocket, because America’s currency will have been debased against the will of its central banks, and will now be at the whims of the President.

And you may say “that’s fine, I like Biden as President” but do you like DeSantis? Do you trust that DeSantis wouldn’t be willing to send his own troops to force his will on the Fed? Would you buy a 10-year government bond if there’s a chance that DeSantis or Trump will be controlling it 2 years? And furthermore, Powell’s remarks on inflation will become worthless. Maybe Biden doesn’t like the rate rising that Powell needs to do, or maybe when the election comes he wants to juice the economy. So what’s to stop him from leaning over and reminding Powell who’s boss? What’s to stop Trump or DeSantis from doing the same? People like Grey once griped that Trump’s complaining caused the Fed to pause rate rises in 2019 (ignoring of course that inflation went under the Fed’s 2% target, which should cause them to pause rate hikes all on its own). Now Grey wants to make the Fed wholly subsumed by the President, so Trump would be able to do whatever he wanted.

Once you’ve sent troops to the Fed, you can’t unring that bell. Investors invest in American Dollars and American bonds in large part because they trust the Federal Reserve to do its duty with regards to the currency. Shattering that trust with soldiers would shatter investor confidence in the American economy as a whole. You’d have a trillion shiny dollars, but they wouldn’t be worth a pence.

Quick post: naysayers aren’t always wrong

There was recently a nuclear fusion “breakthrough” which brought the naysayers out of the woodwork. The breakthrough claimed that scientists had used fusion to generate more energy than was put in. This claim, however, discounted the energy cost of the lasers used to achieve the fusion, which is like saying your company is profitable is you ignore all the salaries. Not only that, this breakthrough isn’t even on the way to creating a self-sustaining fusion reaction, it can not create a self-sustaining reaction due to the need to add and target new material in between each laser pulse. This “breakthrough” is seeming more and more like a nothingburger, and the naysayers have come out to say nay on it.

This has led to the usual backlash from the yaysayers: “they said at airplanes and steamships would never work! You’re ignorant if you don’t believe fusion won’t work!” It’s true that naysayers often laugh and disparage the geniuses of the age, they laughed at the Wright Brothers, they laughed at Edison, but remember they also laughed at Bozo the clown. Yaysayers don’t ever seem to acquiesce to the numerous promised technologies that never really worked, only focusing on those that did work and claiming a direct connection to the current one. So I thought I’d illuminate some prior failures.

Flying cars: everyone knows that the promise of flying cars never panned out despite much public mindshare and media hype. You may counter that “flying cars aren’t impossible, trying to make them is just expensive, difficult, and unnecessary” to which I say “perhaps so is fusion.” The possibility of making a toy-flying car which would never be road-legal is akin to using 300 megajoules to get 3 megajoules out of a fusion pellet, and claiming you have a breakthrough. Doable yes, but it doesn’t prove the endeavor to be doable at scale.

Antigravity elevators. Albert Einstein made several attempts at unifying the (then known) forces of the Universe together. When he started, physicists only knew about electromagnetism and gravity, but it was very enticing that these forces act so similarly in that they have infinite range and their power falls off with the square of the distance. Einstein and others theorized that there was some way to change electricity into gravity and vice versa, and charlatans/”inventors” jumped on the idea. One theory was an antigravity elevator which, by transporting passengers up and down through gravity waves instead of a moving cab, would be much more efficient and perhaps easier to maintain. Of course this idea never came to pass, not least because theories on the unification of gravity with electromagnetism were still missing half the puzzle: the strong and weak nuclear forces.

And here’s a great one: Supersonic flight transport aircraft. Now this might seem a weird one, Concorde showed it isn’t impossible, but as I’ve discussed before history has shown it to be clearly uneconomical when compared to its competitors. An idea doesn’t have to be impossible to get tossed aside, merely uneconomical.

I feel like people don’t realize how many seemingly great ideas have come and failed because they just aren’t economical even if they aren’t impossible. Fusion could well be one of those ideas, sure it works in physics but in economics who’s to say fission and renewables aren’t just objectively better? We’re still decades off even a working test reactor, and the one being planned is already about 4x over budget. Private companies have claimed they’ll come in and disrupt the industry but we had the same claims about a lot of failed projects over the years, who’s to say fusion will be any different? I know that fusion power as a scientific concept is perfectly sound, but as an engineering challenge or a profitable industry I remain skeptical.

Invest in what you know? How much do I need to know?

I’m a biochemical scientist. I’ve published papers. I’ve got degrees. As an investor, I’ve often been given the advice (whether from friends or randos on the internet) that to “invest in what you know” is the safest kind of investment. For me personally though, I’ve avoided investing in any particular biotech or med-tech companies outside of passive ETFs, because I feel like while I know a lot about biochemistry in general I don’t know enough in specific to have any kind of advantage in those areas. I know about Alzheimer’s disease, but I don’t know much about pharmacology so how would I discriminate between two Alzheimer’s drug companies I wanted to invest in? I know about CRISPR/Cas, but I don’t know enough about its delivery system in humans to feel confident that I could pick the winners in today’s more crowded CRISPR field. There are a lot of areas of biology that I feel I have a little knowledge, but not enough to give me an edge.

Maybe there’s a Dunning-Kruger effect here though, because while I can’t explain what cloud computing is besides “it’s like renting another person’s computer,” I have thrown a bunch of money into Microsoft and been happily watching it grow. I like my Microsoft products and my office suite, so I feel good enough about them that I feel they’re doing alright. Yet I clearly know a hell of a lot less about Microsoft than I do any of the biotech companies of the world, so why do I feel so confident investing here?

I don’t know, it’s hard to psycho-analyze myself, but am I making all the wrong moves? Should I focus on investing in biotech companies, confident that my background would give me an edge in picking the winners and avoiding the losers? For now, ETFs for me I guess, but I’ll keep blogging about them since they’re fun.

The nuclear fusion breakthrough that wasn’t

There was recently a nuclear fusion “breakthrough” which I just had to check out. I was disappointed to learn that this wasn’t a breakthrough at all, but a clever bit of marketing dressing up a modest scientific experiment. To explain what happened, a laboratory used around 300 megajoules of energy to create a 2 megajoule laser pulse. That pulse then hit a pellet of material, releasing 3 megajoules of energy as the pellet underwent nuclear fusion. The holy grail of fusion is a self-sustaining reaction, one necessity of such a reaction is that more energy must be released than is put in, and this experiment was hails as doing just that since the 3 megajoules of released energy is more than the 2 megajoule laser pulse. Yet that isn’t actually true because 300 megajoules went into creating that laser pulse, this is like saying a company is profitable if you ignore all salary costs. At the end of the day we want to develop a fusion reaction such that energy out > energy in, and this reaction simply did not do that.

I know why they tried to spin it this way, it’s a longstanding trick of pulsed-laser experiments to report only the amount of energy delivered by the laser, ignoring the amount of energy it takes to create that laser pulse. It makes your reactions seem a lot more efficient and feasible than they really are. But this kind of lying does the entire industry a disservice because it’s just more evidence on the pile of fusion-boosters overpromising and underdelivering. Reading this news you’d mistakenly believe we are now on the precipice of economical and available fusion power when in actuality we’re about as far as we’ve always been.

Rest in Peace, Shamus Young

Yesterday, I wrote a post where I offhandedly mentioned the death of Shamus Young.  I had done so because during the post I remembered a decade old post of his (that I still can’t find!) that had so succinctly explained everything I was talking about.  I finished the blog post, and while looking for Shamus’ post so I could link to it, I learned that he had died last year. 

I’m pretty late to the party on this one, I haven’t been following him for a few years.  But I first heard about him when he published DM of the Rings around a decade and a half ago, and for a while he was my main source of gaming news and reviews.  I first played Oblivion because of a post he wrote about it, same with Morrowind and even the original X-Com.  I got a lot of my early gaming exposure from him and his blog, and I still think a lot about some of the things I read from him.  My previous post on Skyrim is based heavily on a post I remember him writing about Oblivion and RPGs in general, and a lot of the concepts he wrote about still come back to me.  Learning that he had passed, at what seems like an early age, kind of hits me.  I was never more than a lurker to his blog, and I don’t really know what I wanted to say with this post.  I’m so late to the party and was no more than a reader, so I can’t really share in the grief with others.  But I just wanted to say that he was incredibly fun and funny, and I’m glad I got to read him.

If you’ve never read it, DM of the Rings is well worth your time.  Farewell to a really cool guy.

The circle of Skyrim

This probably won’t be controversial, but The Elder Scrolls: Skyrim is a pretty good game. For what it is, I’d say it’s a masterpiece. There’s certainly some parts I don’t enjoy, (the guild quests can be lame, the main plot meanders, the civil war is undercooked), but none of those bring down the enjoyment of what Skyrim actually is. Skyrim is a time waster, expertly designed and developed to have you spend hours upon hours without even realizing you’re doing so, ensuring that at any moment there are 5 different activities you could be doing and a dozen different goals you could be working towards. I remember first thinking about this topic due to a post written by the late Shamus Young, but I can’t remember the exact post so I’m sorry I cannot link directly. Here’s how a few hours of Skyrim may play out:

  • Load up the game and dive into some dungeon. There’s tons of the map and the combat is engaging enough to make this enjoyable. You may even get some nice loot depending on where you dive: rare materials, dragon souls, even a Word Wall to give you new powers
  • With the dungeon now thoroughly dived, make your way back to town. It’s here that the time wasting really begins. You can sell your loot to merchants, use the proceeds to buy better gear or a house in town. You can buy training in a skill, unlocking more perks you can use out in the world. There are 3 different crafting-based skills and your loot may well suit all 3, so you can run around town crafting new weapons and items with the loot you acquired. These and other time sinks give you ways to keep strengthening your character, making you better able to head back into the world and fight.
  • DING! You leveled up! Since Skyrim uses the “learn by doing” system of level-ups, just crafting stuff will advance your skills and earn you new perk points, which can be spent to unlock new abilities
  • New abilities in tow, you may head back out into the world to try them out, plus you have whatever sweet loot you got out of your last dungeon. Maybe you can disarm opponents now thanks to a Word Wall you found, plus maybe you have a fancy new Dwarven Blade courtesy of the Smithing perk you just bought.
  • Having now dived a few more dungeons you may be getting bored with the combat, new perks or no. Fear not, the game still has ways of entertaining you, in town you may learn of an interesting new quest which could break up the monotony of combat, or decide to join one of the factions for a different flavor of gameplay. The factions themselves will give you a bit of story and their own quests, again breaking up the monotony and keeping you engaged even if all you’re doing is running around doing more fighting and gathering more loot.
  • And since you’re doing more fighting and gathering more loot, you need to keep heading back into town, spending more time running about the shops and skill trainers, leveling up further and further and buying more and more new cool abilities to try out in the world
  • And the world itself may have fun quests. Go into a random dungeon? Hey there’s a guy here wanting to kill the people looting his family’s crypt. Well that’s what I was just about to do, but I’ll fight on the side of justice this time. These quests out in the world do even more to frame the repetitive fighting and make it still feel “fresh” even as you hack your 1000th bandit to pieces. You may be doing the same thing over and over again, but it never really feels like it
  • And the maximum carry weight even feeds into this. We all know how much it sucks to be overencoumbered with all your loot, but that’s a GREAT incentive to head back into town to sell or use it all, again letting you spend time there, power up, and again want to go back out into the world.

Skyrim does an amazing job at making a super simple combat and leveling system keep you engaged for hours. The fact that every moment feels fresh and new, and the fact that every activity pushes you towards doing other activities, is a testament to how fun the game is. Running around town makes me want to use my new gear and go dungeon diving, gathering a bunch of loot in dungeons makes me want to go back to town and cash it in. The quests and questlines are all enjoyable enough to make the umpteenth Draugr crypt still feel engaging, and there are enough memorable characters sprinkled around the make the world feel real and alive. I only write this post because I just lost an entire weekend to Skyrim, and I hope I can get this game out of me so I can get back to work later, but this decade old game is still really really good.

Maker vs Taker states

Last year, Elon Musk paid over 11 billion dollars in income tax, more than the amount paid by every single person I know COMBINED. Yet for all that I have no desire to see him get special privileges, or to have his complaints be heard over other people’s. I know we live in the real world where money buys access, but we should all strive to live in a better world where all are presumed equal regardless of wealth. So if Elon Musk shouldn’t get special favors, why should California or New Jersey?

California and New Jersey have been described as “maker” states, in comparison to “taker” states like Mississippi and New Mexico. California and New Jersey residents pay much more to the federal government than their state collectively receives, and vice versa for Mississippi and Mexico. This has led some lawmakers, like Josh Gottheimer (D-NJ) to call out the “moocher” states, and say that laws should be written to benefit the people of his “maker” state, by lowering their tax burden or enacting their preferred policies.

I’ve seen this exact line of reasoning before all across social media. When Republicans complain about the priorities of the government, Democrats come out of the woodwork to say that since blue states pay more tax, red states need to shut up and put up. Yet this is an absurd, Romney-esque line of reasoning that would have been utter heresy in 2012, the idea that wealthier groups of people should be heard over the voices of poorer groups. The next time Gottheimer complains about Musk, will he remember to shut up and put up since Musk pays more taxes than almost his entire state populations combined?

I think this belies the maddening hypocrisy of the maker/taker argument, it was true when Romney said it and it’s true when Gottheimer and lefties online say it. There is ALWAYS someone richer than you, and if you wouldn’t bend the knee to them then no one should bend the knee to you. Furthermore we live in a democracy, one man one vote. The votes of the poor carry just as much weight as the votes of the rich, and there is no special provision that says otherwise. That goes for poor people just as much as poor states. If Democrats want to be the party of the people, I’d better never hear another one of them insinuate that rich voters matter more than poor voters.

Beam Therapeutics: what’s so special about prime editing?

Beam Therapeutics is another biotech company often mentioned in the same vein as Ginkgo Bioworks, Amyris, and Twist Bioscience, and since I’ve blogged about all three of those I might as well blog about Beam. Unlike Ginkgo and Twist, Beam isn’t a shovel salesman in a gold rush, they’re actually trying to create drugs and sell them, in this case they’re trying to break into or perhaps even create the cutting edge industry of medical genetics, changing people’s genes for the better. I’ll briefly discuss the science of their technology, but I feel like the science surrounding their technology deserves the most focus.

Beam has a novel form of CRISPR/Cas gene editing called prime editing. In both normal CRISPR/Cas and prime editing, genetic information is inserted into a living organism by way of novel DNA, guide-nucleotides and a DNA cutting enzyme. The guide-nucleotides direct the information to the specific part of the genome where it is needed, the DNA cutting enzyme excises a specific segment of host DNA, and hopefully DNA repair mechanisms allow the novel DNA to be inserted in its place. These techniques always rely in part of the host’s own DNA repair mechanisms, you have to cut DNA to insert novel DNA and that cut must then be stitched back up. Most CRISPR/Cas systems create double-stranded breaks while prime editing creates just single stranded breaks, and this greatly eases the burden of the host DNA repair mechanisms allowing inserts to go in smoothly and with far less likelihood of catastrophic effects. Double stranded breaks can introduce mutations, cancers, or cause a cell to commit cell-suicide to save the rest of the body from its own mutations and cancers. Because Beam is using prime editing, their DNA editing should have less off-target effects and far less chances to go wrong.

So the upside for Beam is that they’re doing gene editing in what could be the safest, most effective way possible. The downside is that gene editing itself is still just half the battle.

When I look at a lot of gene editing companies, I quickly find all kinds of data on the safety of their edits, the amount of DNA they can insert or delete, and impressive diagrams about how their editing molecules work. I rarely see much info about delivery systems, and that’s because delivering an edit is still somewhat of an Achilles’s heel of this technology. In a lab setting you can grow any cell you want in any conditions you want, so delivering the editing machinery (the DNA, the guide-nucleotides, the enzymes) is child’s play. But actual humans are not so easy, our cells are not readily accessible and our body has a number of defense mechanisms that have evolved to keep things out and that includes gene editors. To give you an idea of what these defenses are like, biology has its own gene editors in the form of retroviruses which insert their DNA into organisms like us in order to force our body to produce more viral progeny, a process which often kills the host. Retroviruses package their edit machinery in a protein capsid which sometimes sits inside a lipid (aka fatty) envelope, and so the human body has a lot of tools to recognize foreign capsids and envelopes and destroy them on sight. These same processes can be used to recognize and destroy a lot of the delivery systems that could otherwise be harnessed for gene editing.

Some companies side-step delivery entirely, if it’s hard to bring gene editing to cells why not just bring the cells to gene editing. This was the approach Vertex Pharmaceuticals used in its sickle cell anemia drug, blood stems cells were extracted from patients and edited in a test tube, before being reinserted into the patients in order to grow, divide, and start producing non-sickled red blood cells. This approach works great if you’re working on blood-based illnesses, since blood cells and blood stem cells are by far the easiest to extract and reinsert into the human body. But for other illnesses you need a delivery method which, like a virus, is able to enter the organism and change its cells’ DNA from within.

So if Beam Therapeutics wants to deliver a genetic payload using their prime editing technology, they’re going to need a delivery system which obeys the following rules

  • It must be able to evade the immune system and any other systems which would degrade it before it finds its target cells
  • It must be able to be targeted towards certain cells so that it doesn’t have off target effects
  • It must be able to enter targeted cells and deliver its genetic package

So let’s look at the options.

Viruses have already been mentioned, and they can be engineered in such a way as to deliver a genetic package without causing any disease. However as mentioned they are quickly recognized and dispatched by the immune system whenever their are found, their protein shells being easy targets for our bodies’ adaptive immune system. Normal viruses get around this by reproducing enough to outcompete the immune system that is targeting them, but we don’t want to infect patients we just want to cure them, so using viruses that reproduce is off the table for gene editing.

A variety of purely lipid-based structures exist which can ferry a genetic package through the body. Our cell membranes are made of phospholipids, and phospholipids will naturally form compartments whenever they are immersed in water. Phospholipids also have the propensity to fuse with each other, allowing their internal compartments to be shared and anything inside them to move from one to the other. Packaging a gene editor inside phospholipids would be less likely to trigger the immune system, and they can be created in such a way that they target a particular cell type to deliver their genetic package. However random phospholipids can be easily degraded by the body, limiting how long they can circulate to find their target cell. Furthermore their propensity to fuse is both a blessing and a curse, allowing them to easily deliver their genetic package to targets but also making them just as likely to deliver it to any random cell they bump into instead. This means a lot of off-target delivery and the possibility for plenty of off-target effects

At the other end of the scale are nanoparticles made of metals or other compounds. Many methods exist to attach drugs to the outside of a nanoparticle and target that nanoparticle to a cell, however this in turn leaves the drug free to be interacted with and targeted by the immune system. For many drugs this is fine, but prime editing uses foreign proteins, DNA and free nucleotides and the body is downright paranoid about finding those things hanging around since that usually means the body has either a cancer or an infection. To that end, the body destroys them on site and triggers an immune response, which would severely curtain any use of nanoparticles to deliver a genetic package. Nanoparticles can also be designed hollow to allow for the prime editing machinery to fit snugly inside them, but this can lead to the machinery just falling out of the nanoparticle in transit and being destroyed anyway. You might say “well not a hollow sphere that fully surrounds the machinery so it can’t fall out?” But it does need to get out eventually if it wants to edit the cell, and if it’s encased in a solid sphere of metal it can’t do that. Enzymes to breach the metal would be cool but are impractical in this case.

Between these two extremes we have a number of structures made of lipids, proteins, polymers or metals, and they all struggle with one of these points. They can’t encase the machinery, or they can’t easily deliver the machinery, or they trigger an immune response, or they degrade easily, or they often cause off-target delivery. Delivery to the target is Step 0 of both prime editing and gene editing in general, and for the most part this step is still unsolved. I’ve visited several seminars where viral packages for delivering CRISPR/Cas systems were discussed, and while these seem some of the most promising vectors for gene editing they still have the problem of triggering the body’s immune system and being destroyed by it. The seminars I’ve watched all discussed mitigating that problem, but none could sidestep it entirely.

I do believe that Beam therapeutics has technology that works, their prime editing is clearly a thing of beauty. Beam is currently working on treatments for sickle cell anemia, as is Vertex Pharmaceutical, and as are most gene editing companies because it’s a blood-based disease that is amenable to bringing the cells to the gene editing machinery instead of having to go vice versa. But for anything where you can’t bring the cells to the editing, Beam isn’t quite master of it’s own fate because for prime editing to reach the cells of the body it will need to be delivered in some way and currently that’s an unsolved problem. Even a system that works to deliver some packages won’t necessarily work for all of them as size and immunity considerations change with the specific nature of the genetic package you’re delivering. I would also be worried about Beam’s cash burn, they are essentially pre-revenue and will need to do a lot of research before any of their drugs get to market or can be sold to a bigger player. I think they can survive for a long while by selling stock since their price has held up a lot better than other biotechs I’ve blogged about, but that’s good for them and not for a shareholder. As long as interest rates keep going up, I’ll treat pre-revenue companies with a wary eye.