There's Plenty of Room at the Bottom

Friday's Wall Street Journal had a piece in the back opinion section (which has items about culture & religion and similar stuff) discussing Richard Feynman's famous 1959 talk "There's Plenty of Room at the Bottom". This talk is frequently cited as a seminal moment -- perhaps the first proposition -- of nanotechnology. But, it turns out that when surveyed many practitioners in the field claim not to have been influenced by it and often to have never read it. The article pretty much concludes that Feynman's role in the field is mostly promoted by those who promote the field and extreme visions of it.

Now, by coincidence I'm in the middle of a Feynman kick. I first encountered him in the summer of 1985 when his "as told to" book "Surely You're Joking Mr. Feynman" was my hammock reading. The next year he would become a truly national figure with his carefully planned science demonstration as part of the Challenger disaster commission. Other than recently watching Infinity, which focuses around his doomed marriage (his wife would die of TB) & the Manhattan project. Somehow, that pushed me to finally read James Gleick's biography "Genius" and now I'm crunching through "Six Easy Pieces" (a book based largely on Feynman's famous physics lecture set for undergraduates), with the actual lectures checked out as well for stuffing on my audio player. I'll burn out soon (this is a common pattern), but will gain much from it.

I had never actually read the talk before, just summaries in the various books, but luckily it is available on-line -- and makes great reading. Feynman gave the talk at the American Physical Society meeting, and apparently nobody knew what he would say -- some thought the talk would be about the physics job market! Instead, he sketched out a lot of crazy ideas that nobody had proposed before -- how small a machine could one build? How tiny could you write? Could you make small machines which could make even smaller machines and so on and so forth? He even put up two $1000 prizes:

It is my intention to offer a prize of $1,000 to the first guy who can take the information on the page of a book and put it on an area 1/25,000 smaller in linear scale in such manner that it can be read by an electron microscope.

And I want to offer another prize---if I can figure out how to phrase it so that I don't get into a mess of arguments about definitions---of another $1,000 to the first guy who makes an operating electric motor---a rotating electric motor which can be controlled from the outside and, not counting the lead-in wires, is only 1/64 inch cube.

The first prize wasn't claimed until the 1980's, but a string of cranks streamed in to claim the second one -- bringing in various toy motors. Gleick describes Feynman's eyes as "glazed over" when yet another person came in to claim the motor prize -- and an "uh oh" when the guy pulled out a microscope. It turned out that by very patient work it was possible to use very conventional technology to wind a motor that small -- and Feynman hadn't actually set aside money for the prize!

Feynman's relationship to nanotechnology is reminiscent of Mendel's to genetics. Mendel did amazing work, decades ahead of his time. He documented things carefully, but his publication strategy (a combination of obscure regional journals and sending his works to various libraries & famous scientists) failed in his lifetime. Only after three different groups rediscovered his work -- after finding much the same results -- was Mendel started on the road to scientific iconhood. Clearly, Mendel did not influence those who rediscovered him and if his work were still buried in rare book rooms, we would have a similar understanding of genetics to what we have today. Yet, we refer to genetics as "Mendelian" (and "non-Mendelian").

I hope nanotechnologists give Feynman a similar respect. Perhaps some of the terms describing his role are hyperbole ("spiritual founder"), but he clearly articulated both some of the challenges that would be encountered (for example, that issues of lubrication & friction at these scales would be quite different) and why we needed to address them. For example, he pointed out that the computer technology of the day (vacuum tubes) would place inherent performance limits on computers -- simply because the speed of light would limit the speed of information transfer across a macroscopic computer complex. He also pointed out that the then-current transistor technology looked like a dead end, as the entire world's supply of germanium would be insufficient. But, unlike naysayers he pointed out that these were problems to solve, and that he didn't know if they really would be problems.

One last thought -- many of the proponents of synthetic biology point out that biology has come up with wonderfully compact machines that we should either copy or harness. And who first articulated this concept? I don't know for sure, but I now propose that 1959 is the year to beat

The biological example of writing information on a small scale has inspired me to think of something that should be possible. Biology is not simply writing information; it is doing something about it. A biological system can be exceedingly small. Many of the cells are very tiny, but they are very active; they manufacture various substances; they walk around; they wiggle; and they do all kinds of marvelous things---all on a very small scale. Also, they store information. Consider the possibility that we too can make a thing very small which does what we want---that we can manufacture an object that maneuvers at that level!

So if the nanotechnologists don't want to call their field Feynmanian, I propose that synthetic biology be renamed such!

Young Men & Fire

60 years ago today, 15 young men floated out of a Montana sky onto rugged ground below. They were there to join another already on the scene of a small forest fire. Within a few short hours, only 3 of those men would not be fatally burned by that same fire. As deserved as the festivities are over the spectacular events of July 1969, it's a pity that so little attention has been paid to this tragedy 20 years earlier.

I was in college when I first read the definitive account of the Mann Gulch fire, Young Men and Fire by Norman Maclean. Given that I was about at the same age at the time as those smokejumpers, it had a lot of resonance for me. It remains one of my favorite books (along with his other masterpiece, A River Runs Through It, and Other Stories). Someday, I hope to hike the gulch, both to enjoy the beauty and to contemplate the sacrifices there.

It might seem like this doesn't have much to do with science (it certainly has nothing to do with genomics!), but there's more than a little of it in his science. YM&F covers a lot of what was known then and was found later about the science of wildfires and one of it's first students, Harry Gisborne. Maclean himself was never trained as a scientist, but had a keen eye for nature from spending so much time in it. River contains more than a little bit of the science of fish & fishing streams. Maclean himself led the last two survivors of the fire on a visit to the site decades later that turned up critical artifacts from that night. The Mann Gulch tragedy has also become a case study in how organizations respond to extreme stress.

Another great connection between Maclean & science, only barely touched on in Young Men, but treated in expanded form in another article (reprinted in The Norman Maclean Reader). As a young graduate student at the University of Chicago, Maclean had become an acquaintance of the great physicist Albert Michelson, and Maclean in the longer piece writes lyrically about Michelson's lifelong quest to precisely measure the speed of light. It's a gem of scientific journalism.

I'll leave with a quote from Michelson via Maclean, which I love. Michelson was brushing off a compliment from Maclean on the elder man's billiards playing

Billiards, though, is a good game, but billiards is not as good a game as chess. Chess, though, is not as good a game as painting. But painting is not as good a game as physics.

Clearing the bookshelf

My email box recently resembled the scene in the first Harry Potter book where the boy learns his true heritage. The torrent of messages did not arrive by owl, but were from someone trying to reach me with important news: I was holding a heap of overdue library books.

Alas, I can't claim to have read them all. I don't get to the public library as often as I would like, but when I get there I tend to bring back a bunch. I'm a sucker for books in the rack or end-of-aisle displays, plus I tend to get a big cluster of books in one subject area to see which I like. Throw in the ability to request books from virtually anywhere at anytime via the Internet, and it can really be feast-or-famine.

One of the books which was overdue was one I had to wait on, How Doctors Think by Jerome Groopman. This is a book everyone should take a stab at. First, it is an interesting analysis of how people think; while it is in a medical context, many of the pitfalls and strategies he explores are relevant everywhere. Second, most if not all of us will be patients at some time, or interested parties in the medical care of loved ones. By understanding the mental traps doctors can fall into, patients & patient advocates can better assist doctors in their care and recognize when the doctor is not a good match for the patient or the problem.

Groopman also comes across as a real mensch. He seems like the sort of person you'd try to grab at departmental tea or after a seminar -- and he'd actually speak with you. I certainly didn't agree with all his conclusions in the book, but I could see enjoying any discussion he might bring forth. He is also honest about when he has himself fallen into traps, such as his own arthritis coloring his early evaluation of COX-2 inhibitors (he wrote an article in a national lay magazine touting them as super aspirin).

Another overdue book was Rosalind Franklin: The Dark Lady of DNA. I started reading it on the supposition that most of what I knew about Franklin was from Watson's books, which seemed embarassing. I later realized that I had also read Eighth Day of Creation, so some balance was already there. The book does a good job of laying out her many contributions in crystallography, why the time of the race for the double helix was completely awful for her, and the many challenges of being a Jewish woman scientist in English scientific labs of the 40's and 50's.

My one complaint with the book is that while it shows her famous diffraction photograph of DNA, the book (and probably every other one I've ever seen with the photo) lacks any of the prior photos for comparison. It would also be interesting to see the unpublished manuscript on the DNA structure that Aaron Klug later unearthed, to see how close she was to the solution when Watson & Crick scooped it away. On the point of how they did it, there is no extreme skullduggery discussed here: just a clueless Maurice Wilkins leaking the key data to an opportunistic Watson. It is also interesting to better understand the collaborations she had with each of W&C after the helix; it would seem that professionally she didn't see them as thieves of her glory.

One interesting speculation that hit me early on and is discussed late in the book. Franklin's life was cut short by ovarian cancer. I hadn't realized she was from an Ashkenazi background, a heritage that is unfortunately at higher risk than other populations of carrying BRCA mutations. Alternately, many who saw her work describe her as being particularly unworried by safety precautions around the X-ray beams, though to some degree this was common & their recollections may be colored by her outcome.

Alas, one book that got back unread was Invisible Frontiers, the story of the race to clone insulin. I read it as a senior in college, but it is really due for a re-read. One could imagine staying quite busy just reading biographies around the double helix : I'm really due to re-read Watson, Wilkin's autobiography is wait-listed, and Crick's autobiography somehow was in an earlier batch of books held (but not read) until overdue.

And then there are those owls; having now finished the last book in the series & read the first (and started the second) with my little wizard, the temptation is there to jump ahead and re-read the rest to better understand all the characters & threads woven in the last book. Alas, there still aren't any good clues to the genetics of Mugglery.

Psst! Hot Stock Tip! This company is going to be average!

The last two days have been active on the NASDAQ for the old stomping grounds. Prior to the trading day yesterday a stock analyst upgraded the stock, and MLNM gained about 6% on the day with a trading volume significantly (but less than 2X) above average volume. Today, the company announced some positive results in front-line multiple myeloma treatment, and the stock again turned over 5M+ shares but just nudged up a bit.

What is more than a little funny about yesterday is what the analyst actually said: instead of 'underperforming' the market, he expected Millennium to "Mkt Perform" -- that's right, that it would be exactly middling, spectacularly average, impressively ordinary. Indeed, he put a target on the stock -- $10, or a bit less than what it was selling for that day. For that he was credited with sparking the spike.

What's even more striking is that the day before another investment house downgraded Millennium from 'Overweight' to 'Equal weight'. Each company picks its own jargon, but this is really agreeing -- they both predict Millennium to do as well as the market. Oy!

Far more likely a cause in the spike was leakage of the impending good myeloma news. I've never looked systematically, but good news in biotech seems to be preceded by trading spikes as much as it is followed by them. Periodically someone is nailed for it (and not just domestic design goddesses), but there is probably a lot of leakage that can never be pursued.

I'm sure there are a lot of smart people earning money as stock analysts who carefully consider all the facts and give a well-reasoned opinion free of bias, but they ain't easy to find. For a while I listened to the webcasts of Millennium conference calls, but after a while I realized that (a) no new information came out and (b) some of the questions were too dumb to listen to. Analysts would frequently ask questions whose answer restated what had just been presented, or would ask loaded questions which were completely at odds with the prior presentation. How the senior management answered some of those with a straight face is a testament to their discipline; I would have been lucky to get by with a slight grimace. Some analysts were clearly chummy with company X, and others with company Y, and little could change their minds.

If you look at the whole thing scientifically, the answer is pretty clear: listening to stock analysts is a terrible way to invest. If you want average returns, invest in index funds. If you want to soundly beat the averages, start looking for leprechauns -- their pots of gold are far more plentiful than functional stock picking schemes. Buy a copy of 'A Random Walk on Wall Street' and sleep easy at night. Yes, there are a few pickers who have done well, but they are so rare they are household names. Plus, there are other challenges: Warren Buffett has an impressive track record, but if he continues it until my retirement his financial longevity will not be the point of amazement.

Disclosure: somewhere in the bank lock box I have a few shares of Millennium left -- I think totaling to about the same as the blue book value on my 11-year old car (though perhaps closer to the eBay value of my used iPod). The fact they are in a bank protected them from the grand post layoff clean out.

Two more farewells

Today's paper's obituaries brought the news of Stanley Miller's passing. Miller's experiment with Harold Urey is notable for many reasons. First, it sparked the whole field of abiogenesis, and second it is recognizable to many persons outside of biology or chemistry. Indeed, there used to be a video at the National Air & Space Museum of Julia Child running the experiment, cooking primordial soup (I think the video can be found in some libraries). Miller's experiment did not prove abiogenesis, nor did it prove a particular model, but it did demonstrate that interestingly complex organic compounds could be generated from simple processes that might have existed on a pre-life Earth. Indeed, it is the fact that Miller's work stimultated debate & testing about what the prebiotic Earth was or was not like, the hallmark of good science on the outer fringe.

The obituary also noted that Miller's thesis advisor, Nobel Laureate Harold Urey, insisted that he be sole author on the paper. I've always known this as the Miller-Urey experiment, but that was awfully gracious of a senior scientist, and a model not always followed. At my department at Harvard there was a story of a graduate student whose defense was snubbed by his advisor due to a dispute about failing to include the advisor on a submitted paper.

I've been meaning to note one other passing of a great pioneer. In The Right Stuff, there is a scene of the potential Mercury astronauts enduring an exhalation test, and at the end only Scott Carpenter & John Glenn are still blowing bubbles. That is now the case in real life with the passing of Wally Schirra. Schirra was notorious as a jokester, but it is also notable that when it came time to name his capsule, he picked Sigma 7, for the letter's relevance to math, science & engineering. His sigma was indeed spectacular, splashing down within sight of his recovery craft. As a kid I never understood why Schirra retired just before he would have had a lock on a slot to go to the moon. As an adult, I can begin to fathom how exhausting all the training was.

Farewell Kilgore Trout

The passing this week of Kurt Vonnegut was strongly felt here, as he is one of my favorite authors. I first was keyed into Vonnegut by a high school English teacher (by the name of French!) and started reading a few. When I got to college, I started plowing through the whole shelf of Vonnegut novels & catching his few last ones as they came out. If you've never savored the ever-relevant bitter humor of Mother Night or the absurdity of Cat's Cradle, you're missing out. Breakfast of Champions & Sirens of Titan are great fun too, and even the lesser works have lots of good bits in them. Vonnegut isn't for prudes, though has texts are really pretty tame compared to a lot of other literature before and after (e.g., my current soul-enriching time sink, The Good Soldier Svejk -- now there is some inspired vulgarisms!)

Please don't take this the wrong way, but I enjoy reading good obituaries. Not that I'm happy to see someone pass, but good obituaries teach you something you didn't know -- perhaps because you never knew the person existed (but should have), but other times because you didn't know something interesting about a familiar figure. I never knew that Vonnegut had studied to be a biochemist. I think Asimov was also originally a biochemist as well -- but surely to group them in this way is to engage a granfalloon. Hi Ho!

454? How Roche!

Today's GenomeWeb bears the news that Roche Diagnostics is buying out 454 Life Sciences. Since Roche was previously the sole distributor of 454's sequencers and Curagen had announced their desire to sell the subsidiary, this is hardly a shocking development. But it is the third next generation sequencing company to be bought by an established player -- ABI slurped up Agencourt Personal Genomics and Illumina recently bought Solexa. So far, Affymetrix and Agilent have stayed out -- as has Nimblegen. There are plenty of other startup next generation sequencing shops out there, and certainly other candidates for acquirers. Roche, of course, got the clear current front runner, though it may be that the next wave of sequencer launches will close the gap quickly.

Whether these acquisitions are good for next generation sequencer development is an open question. On the one hand, these larger organizations bring deep pockets and substantial marketing expertise. But, there are plenty of pitfalls. For both ABI and Illumina, the new machines compete with their old machines -- smart companies see this as inevitable, but many companies completely botch the job due to internal conflicts (as amply documented by Clayton Christiansen in his books). It isn't encouraging that the Agencourt Personal Genomics technology is impossible to find on the ABI website.

It will also be interesting to see how long the 454 moniker lasts -- one hates to see pioneers go, but on the other hand I find naming a subsidiary after the accounting code tres gauche.

An interesting note in the GW item is that Roche was previously prohibited from marketing regulated diagnostics built on the 454 platform. Roche has previously tried to launch some molecular diagnostics -- the D word is after all in their name -- so this is a clear fit. On the other hand, a run on the 454 is reputed to be serious money, so they'll need to either find a very high value application (in a field notorious for antiquated, miserly reimbursement rules) or figure out a way to run lots of tests simultaneously. Given the rather long read lengths of the 454, one approach to the latter would be to use sequence tags near the beginning of the read to identify the original samples.

Another GW item describes some roundtable discussion at a recent meeting on next generation sequencing. The price for a genome in 2010 is still a big question, but a lot of bets are apparently in the $10K-$25K range. Some of the leaders in the field are taking a realistic view of the utility of such sequencers at such a price tag -- if you can scan the most informative SNPs for $1K, then why sequence? I'm guessing that other than a few pioneers (J.Craig is apparently resequencing his genome), there won't be a lot at those prices. On the other hand, cancer genomics is a natural fit, as each genome is different (indeed, each sample probably has many distinguishable genomes) and understanding all the fine molecular details will be valuable. SNP chips can estimate copy numbers, but not tell you how those pieces are stitched together nor find all the interesting mutations.

Even with the price at $1K, sequencing will certainly not be 'too cheap to meter'. Notions of sequencing a big chunk of the human population have appeal, but do we really want to blow another few billion dollars on human sequencing? On the other hand, as I've suggested before, other mammalian genomes may provide a lot of interesting biology for the buck (or bark). What are the most interesting unbagged genomes out there -- that sounds like the topic for another day's post...

Valentine's Reading

Since tomorrow is Valentine's Day, I was going to suggest a good book appropriate to the date. As is often the case, that book suggests some others in a chain until we finally get back to another book appropriate for the day, though unfortunately for that very reason it is not a good book.

The first book presents a small challenge. While I would never consider myself a prude, its title could potentially cause filters everywhere to flag this site as unsuitable for the younger set (I'm sure a lot of elementary school kids read the site fanatically). But, I hate to be one to change content, especially in a book's title. There's nothing actually pornographic about the book, except the cover -- but only if you have six legs & antennae. So, I will write out the title, but you will need to translate one word.

The book is Olivia Judson's Dr.Tatiana's TCTGAANNN Advice to All Creation. The book is structured as a series of letters to an advice column, letters from various creatures perplexed by misadventures in their love life. Fish who wake up a different gender, mice who are sure their mates are cheating on them, etc. While the schtick could have worn thin, I enjoyed it throughout. She uses a lot of humor, but also details the myriad of reproductive strategies found across the animal world (if I remember correctly, some bacteria slip in near the end). Since reading the book, I can't help but read a story on a novel strategy and think: That would make a great Dr. Tatiana letter. I also get warm inside thinking pondering the notion that Dr. Tatiana should be required high school biology class reading. On the one hand, the students might actually want to read the book! Even better would be the reaction of certain folk, who would be having a hard time deciding whether to be more upset about the S word or about the E word sprinkled throughout (Evolution).

Judson turns out to be the daughter of Horace Judson, whose The Eighth Day of Creation is another must read. Eighth Day describes three of the major early thrusts of molecular biology: the assault on the nature of DNA and the genetic code, the quest to understand gene regulation and the first solving of protein structures. I won't claim it is a small book (686 pages -- and not a large typeface!) or light reading, but in many places you can begin to feel the excitement those pioneers felt as they pushed forward and some of the outsized personalities of the scientists. Some biotech books capture this: Invisible Frontiers (about the early days of recombinant DNA work & the race to clone insulin) and The Billion Dollar Molecule (about the founding of Vertex Pharmaceuticals) would fall into that category; two books I read more recently (and have forgotten the titles) failed miserably -- just the facts ma'am (which has something to do with my forgetting the titles).

Eighth Day is the work of a professional author and will weigh down your backpack. For a lighter touch, both physically & intellectually, try James Watson's The Double Helix. It is, of course, a memoir and Watson was willing to say outlandish things. The opening line is a classic: "I have never seen Francis Crick in a modest mood". I got to meet Watson two summers ago at a scientific meeting (it is a great sadness I never got to meet Crick) and he is just as verbally audacious in person. But again, it does give some feel for the excitement of the time and how high feelings ran.

But finally, please DON'T read Watson's sequel, Genes, Girls, and Gamow: After the Double Helix. Perhaps with a good editor it could have been boiled down into something enjoyable to read, but I'm not sure there would be enough left. Watson spends far too much time on his social life -- and particularly his love life (egad! it's in the title!). Valentine's Day or not, the last thing I want to read is an expanded version of anyone's, even one of the towering figures of 20th century science, little black book.

How We Die

Columnist Art Buchwald died last week, after nearly a year of life his doctors did not expect him to have. Buchwald had chosen to avoid the extension of life promised by kidney dialysis, instead choosing to live his last days on his own terms.

Death is not something we like to think about, but in medicine it is a regular reality -- particularly in oncology. For many patients, thnase choices offered by the current state of oncologic medicine are not easy to accept: disfigurement, chemical warfare agents, extreme nausea, hair loss, memory loss, persistent loss of feeling or constant pain, complete ablation of the immune system, etc. Yet, when the other choice is death, how could anyone choose otherwise?

The answer, of course, is complicated, and each person makes their own choice as to their path. A good exploration of this topic is Sherwin Nuland's book, How We Die. Nuland is a wonderful writer, and he uses many personal stories to trace the topic. The first chapter describes the gradual decline of his beloved grandmother. Particularly poignant for me was the story of a friend of his who was diagnosed with cancer. Nuland recommended an extremely aggressive course of treatment. At the end of his life, the friend basically said "thanks for your concern, but please don't do that to anyone else" -- the small amount of time wasn't worth the agonizing side effects. It is a sobering message.

Phage Renaissance

Bacteriophage, or phage, occupy an exalted place in the history of modern biology. Hershey & Chase used phage to nail down DNA (and not protein) as the genetic material. Benzer pushed genetic mapping to the nucleotide level. And much, much more. Phage could be made in huge numbers, to scan for rare events. Great stuff, and even better that so many of the classic papers are freely available online!

Phage have also been great toolkits for molecular biology. First, various enzymes were purified, many still in use today. Later, whole phage machinery were borrowed to move DNA segments around.

Two of the best studied phage are T7 and lambda. Both have a lot of great history, and both have recently undergone very interesting makeovers.

T7 is a lytic phage; after infection it simply starts multiplying and soon lyses (breaks open) its host. T7 provided an interesting early computational conumdrum, one which I believe is still unsolved. Tom Schneider has an elegant theory about information and molecular biology, which can be summarized as locational codes contain only as much information as they need to be located uniquely in a genome, no more, no less. Testing on a number of promoters suggested the theory valid. However, a sore thumb stuck out: T7 promoters contain far more information than the theory called for, and a clever early artificial evolution approach showed that this information really wasn't needed by T7 RNA polymerase. So why is there more conservation than 'necessary'? It's still a mystery.

Phage lambda follows a very different lifestyle. After infection, most times it goes under deep cover, embedding itself at a single location in its E.coli host's genome, a state called lysogeny. But when the going gets tight, the phage get going and go through a lytic phase much like that of T7. The molecular circuitry responsible for this bistable system was one of the first complex genetic systems elucidated in detail. Mark Ptashne's book on this, A Genetic Switch, should be part of the Western canon -- if you haven't read it, go do so! (Amazon link)

With classical molecular biology techniques, only either modest tinkering or wholesale vandalism were the only really practical ways to play with a phage genome. You could rewrite a little or delete a lot. Despite that, it is possible to do a lot with these approaches. In today's PNAS preprint section (alas, you'll need a subscription to get beyond the abstract) is a paper which re-engineers the classic lambda switch machinery. The two key repressors, CI and Cro, are replaced with two other well-studied repressors whose activity can be controlled chemically, LacI and TetR. Appropriate operator sites for these repressors were installed in the correct places. In theory, the new circuit should perform the same lytic-lysogeny switch as lambdaphage 1.0, except now under the control of tetracycline (TetR, replacing CI) and lactose (LacI, replacing Cro). Of course, things don't always turn out as planned.

These variants grew lytically and formed stable lysogens. Lysogens underwent prophage induction upon addition of a ligand that weakens binding by the Tet repressor. Strikingly, however, addition of a ligand that weakens binding by Lac repressor also induced lysogens. This finding indicates that Lac repressor was present in the lysogens and was necessary for stable lysogeny. Therefore, these isolates had an altered wiring diagram from that of lambda.

. When theory fails to predict, new science lies ahead!

Even better, with the advent of cheap synthesis of short DNA fragments ("oligos") and new methods of putting those together, the possibility of becoming the "all the phage that's fit to print" is really here. This new field of "synthetic biology" offers all sorts of new experimental options, and of course a new set of potential misuses. Disclosure: my next posting might be with one such company.

Such rewrites are starting to show up. Last year one team reported rewriting T7. Why rewrite? A key challenge in trying to dissect the functions of viral genes is that many viral genes overlap. Such genetic compression is common in small genomes, and gets more impressive the smaller the genome. But, if tinkering with one gene also tweaks one or more of its neighbors, interpreting the results becomes very hard. So by rewriting the whole genome to eliminate overlaps, cleaner functional analysis should be possible.

With genome editing becoming a reality, perhaps it's time to start writing a genetic version of Strunk & White :-)