Scan barcode
A review by lpm100
The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race by Walter Isaacson
reflective
fast-paced
3.0
Book Review:
"The Code Breaker"
3/5 stars
Some interesting discussions on bioethics, but a fairly low signal to noise ratio
Of the book:
-56 chapters over 483 pages of prose
-Average of 8.6 pages per chapter (short enough to read two of them over a lunch break).
This book really didn't need to be much more than 250 pages. Randy Schilts wrote a similar blow-by-blow book of an episode in history (the beginning of the HIV crisis, in "And The Band Played On") which was actually even longer than this one, but somehow the events were more interesting, likely because they were more relatable.
This book is disproportionately about the research process and academic politics which are of interest to only a very few people.
The book did get more interesting when the author talked about some of the moral/ethical implications of genetic engineering.
1. In some ways, this book is extremely silly.
¶I would say that it could have been cut down by at least 25% just on omission of the author'
s flapping on about "how hard this is for women just because they are women."
News flash: if there is some new ground being broken by some type of people that are (initially) only there in very small numbers--whatever the reason--of course someone has to go first. (No, "Buckwheat" is not a comfortable character for us to remember but somebody had to go first.)
At one point, Isaacson talks about "the media's presentation of scientists as old white men." (p.34). If they are, then so what?
If there was some movement somewhere for black people to become competitive in Advanced Pure Mathematics (As of now, there are probably no more than a dozen black PhDs in mathematics produced per year--and that might even include people who are EdD's masquerading as real mathematicians), then most of the black students would find themselves working with mostly Eastern Asian / Eastern European colleagues and research advisors.
Also, different types of people just have different interests and aptitudes. (This has been talked about in Charles Murray's "Human Diversity" as well as the multiple times that the author mentions James Watson being run out of town on a rail for daring to observe such.)
Is that worth turning into a whole grievance book, or is it enough to just say that..... Somebody has to go first, and there will be some discomfort until it becomes a normal thing.
2. In some ways, the book is just not honest
¶(p.65): Berkeley's tripling undergraduate tuition was not a result of cuts and state funding, but a result of the fact that education is inherently inflationary because it's not subject to market forces. (It was mentioned in the book that Celera sequenced genome for 1/10 the price of laboratories--at a faster rate.)
¶Yes, it is possible to write a book about someone somewhere who just happened to be researching something interesting that was later brought to commercial fruition.
But, in reality, the OVERWHELMING MAJORITY-->99%-- of (scientific) research will be of no impact. (I don't think anyone cares about Organofluorine Chemistry, although it was once a hot area.)
¶These people easily flying from one dream academic job to another and one postdoc to another just is not representative of reality for the heavy majority of people. (See article: "The Mathematics of the PHD Glut.")
¶(p.139) It is not that the advances by Doudna were created ex-nihilo. There were other research teams that were working on similar projects, and CRISPR-Cas9 had been described before, though the enzymes not actually isolated. It is clear that Doudna wanted to publish her research, lest she get "scooped." (p.202) At one point (January 2013), five papers on the same topic were all published in a single day.
¶¶(p.294) "China has one of the world's most controlled societies, and few things happen in clinics without the government's knowledge"
Just .....no.
Chinese people have been finding ways to get around and obstructive government for several thousand years by now. The reality on the ground is not quite the same as official pronouncements.
3. In some ways, the book is not useful/informative.
¶I have been to undergraduate/graduate school and worked in the science lab, and I do know that academics start the ideas and venture capitalists bring them to fruition.
And it would have to be that way, because people who are academics are categorically not the type of people used to finding ways to turn a profit. (And that's no surprise, if you look at the circumstances in any academic institution.)
¶It is well known that a lot of research projects that ultimately bear fruit are happenstance; this group just happens to have one person that knows somebody that specializes in x-ray crystallography of biomolecules.
Second order thoughts:
1. Sure does seem like wherever happening things ARE, black people ARE NOT. The author states as much (p.461) : "But there were very few African americans, either at the conference or on the benches in the various labs I had visited. In that regard, the new life sciences revolution resembles, unfortunately, the digital revolution. If there are not efforts at outreach and mentorship, biotechnology will be yet another revolution that leaves most blacks behind."
And it is true that I think there was only one black person pictured in this book, and all of the biotech companies were started up by Jewish/Chinese/White/ Indian (p.428)/ Arab (p.426)/Armenians (p.442)/ Turks (p.441)
2. I have lots of questions about how correct it is for researchers to leverage state-funded research into companies from which they take all the profits (Ch 28: there are no less than four companies started) It's like double dipping: taxpayers fund glorified government jobs (universities) and then the best ones take all of the profits. Isaacson lets slip the example of Stanford making $225 million by granting biotech licensees to companies (p.232).
3. If you are looking for a realistic picture of academic life for the great majority who manage to even make it there, you will not find it here. (No discussion of the one body problem, nor the two body problem. Nor endless post docs.)
4. Cultural backgrounds of the participants play a big role in the way that these events played out.
-Feng Zhang/ He Jiankui are far from unusual: It is just the Chinese Way to treat information as something that needs to be hoarded and to smile in your face charmingly, and leave out as much information as possible. It would have been a surprise if he didn't try to double cross / outfox his competitors.)
-Charpentier is hardly unique:It is a common thing in places like France and Italy for people to make an entire career bouncing from one postdoc to another (because there are no full-time positions available).
5. There's a lot of discussion about what is patentable, and who can bring what to market. But, apparently there are things such as "biohackers." By making genetic technology easier to handle, it also means that there are more people who will sell people what they want to buy - - even if it may be a bit dubious.
These discoveries can also be easily turned into biological weapons, and so there's that.
6. This book unintentionally ends up being an extension on Hayek's "The Fatal Conceit": governments don't have the power to ban the invention of technology, and only limited power to decide where it goes.
And let us be clear that money will decide where this goes.
7. The case has been made that the cure to genetic engineering capability is more genetic engineering capability because scale effects can lower the cost.
8. If ethicists and bioengineers are worried about not crossing a red line, fear not: It seems like the ONE red line that nobody is willing to cross is to make a connection between race and IQ. James Watson said out loud what everybody already knows, and he lost his position as Chancellor of Cold Spring Harbor and was banished from almost everything else.
9. "Eugenics" is a word that gives people all heated up, and is guaranteed to turn any discussion into Reduction ad Hitlerium. But, with the big business of bioengineering: you can just get ready for it.
And people who have more money will be able to take advantage of it much faster than everybody else.
*******
Synopses:
€€Part I (3-70): A scientist starts out interested in high school, and then she completes a PhD. She's able to make strides in the field (Molecular Biology / Genetics) because she chooses to not go into an oversubscribed area. (DNA vs. RNA).
€€Part II (71-152)): Introduction to "clustered regularly interspaced short palindromic repeats." (CRISPR).
Lots of Sturm und drang about one research group trying to scoop another, and ultimately the beginnings of a tool for gene editing.
€€Part III (153-244):
Gene editing at this point was not new, but unreliable / dangerous. A very lengthy blow by blow description (including personality profiles) of a bunch of scientists trying to scoop one the other to publish information that was discoverable just as a matter of time. Of course, there is lots of academic bickering about who discovered what. Finally, this culminated in a patent lawsuit that dragged on for probably about 8 years.
€€Part IV (245-266):
A brief chapter, deals with therapeutic applications. At this moment, the treatments are cost prohibitive. Something like $1 million per patient. Although, treatments of sickle cell have led to heritable changes.
€€Part V (267-298):
A brief history of the scenarios that involved scientists coming up with agreements as to what should and should not be done as well as what can and cannot be done. Apparently, the American attitude toward genetic engineering was one of great enthusiasm, whereas the Europeans came up with Oviedo Convention ("GMO" is a bad word in Europe--Germany and Britain excepted, for some reason.
€€Part VI(299-334) The first genetically modified babies are made by a Dissolute Mainland Chinese--He Jiamkui.
He thought that he would be a national hero in China, and what he got for his trouble was actually: i)a 3-year prison sentence; ii) $430,000 fine; iii) a lifetime ban from working in reproductive science. All were imposed by the Chinese government.) At this point, the germline is no longer a red line.
€€Part VII (335-370) More moral speculation and thought experiments. The difference between treatment (let's imagine treatment for Huntington's disease) versus enhancement (let's imagine making someone taller). The difference between absolute improvement and a positional improvement. Mood disorders are also associated with creativity. So, if you find a way to engineer them out of existence, what does that mean?
€€Part VIII (371-400) Odds and ends. The author goes into a lab and does an experiment that undergraduates have been able to do for the last 30 years. He revisits James Watson, who was punished for crossing the Red Line of linking race and IQ distributions
€€Part IX (401-477) Covid! Dealing with obstructive bureaucracy, such as the FDA and CDC. (Drugs and tests are regularly finished years before the FDA approves them. Covid created some limited fast-tracking, but the problem still exists.) Dealing with idiot politicians, such as Anthony Fauci. Still more bio companies started by US academics to solve problems that the state bureaucracy cannot.
Factoids:
1. It cost $3 billion to sequence human DNA the first time around.
2. Recombinant DNA was figured out in the early 70s. (By the time I was an undergraduate in the late 90s, it was an experiment that college sophomores could do.)
3. (p.99) Before recombinant DNA, 1 lb of insulin required 8,000 lb of pancreas ripped from 23,000 pigs/ cows.
4. What is the Difference Between CRISPR and Restriction Enzymes? CRISPR-Cas system is a prokaryotic immune system that confers resistance to foreign genetic elements. On the other hand, restriction enzymes are endonucleases that recognize a specific sequence of nucleotides and produce a double-stranded cut in the DNA
5. (ZFN) Zinc-finger nucleases are artificial restriction enzymes generated by fusing a zinc finger DNA-binding domain to a DNA-cleavage domain
6. TALENs are artificial restriction enzymes and can cut DNA strands at any desired sequence.
7. Three companies featured here: CRISPR Therapeutics; Editas Medicine; Intellia Therapeutics.
--2021 respective revenue ($millions): 910, 25.5, 33.1.
--Market cap ($billions): 3.97, 0.66, 3.32
--Net operating ($millions): 371, -192, -267
8. "Biohackers" are a thing. Enter the non-binary freak "Jo(siah) Zayner," stage left.
9. Germline and somatic cells are two different things. The first being what will be inherited and present for all times in the second being cells that exist as of a particular moment for some specified and limited use.
10. The major four infectious agents are: viruses, bacteria, fungi, protozoa.
11. Viral vaccines are of a few types. An attenuated version of the virus. Or a "killed" virus. Or a subunit of the live virus. Covid brought to the fore genetically engineered viruses.
Memorable quote (p.241): "Don't fight over divvying up the proceeds until you finish robbing the stagecoach."
*******
Verdict: I don't know if I recommend this book all that much. If you wanted an idea of the workings of DNA, better that you would read "The Gene" by Siddhartha Mukherjee.
The point of this book is about CRISPRs, and I would say it's probably better to search for another popular book without all of the literary spinach that is contained in this one.
"The Code Breaker"
3/5 stars
Some interesting discussions on bioethics, but a fairly low signal to noise ratio
Of the book:
-56 chapters over 483 pages of prose
-Average of 8.6 pages per chapter (short enough to read two of them over a lunch break).
This book really didn't need to be much more than 250 pages. Randy Schilts wrote a similar blow-by-blow book of an episode in history (the beginning of the HIV crisis, in "And The Band Played On") which was actually even longer than this one, but somehow the events were more interesting, likely because they were more relatable.
This book is disproportionately about the research process and academic politics which are of interest to only a very few people.
The book did get more interesting when the author talked about some of the moral/ethical implications of genetic engineering.
1. In some ways, this book is extremely silly.
¶I would say that it could have been cut down by at least 25% just on omission of the author'
s flapping on about "how hard this is for women just because they are women."
News flash: if there is some new ground being broken by some type of people that are (initially) only there in very small numbers--whatever the reason--of course someone has to go first. (No, "Buckwheat" is not a comfortable character for us to remember but somebody had to go first.)
At one point, Isaacson talks about "the media's presentation of scientists as old white men." (p.34). If they are, then so what?
If there was some movement somewhere for black people to become competitive in Advanced Pure Mathematics (As of now, there are probably no more than a dozen black PhDs in mathematics produced per year--and that might even include people who are EdD's masquerading as real mathematicians), then most of the black students would find themselves working with mostly Eastern Asian / Eastern European colleagues and research advisors.
Also, different types of people just have different interests and aptitudes. (This has been talked about in Charles Murray's "Human Diversity" as well as the multiple times that the author mentions James Watson being run out of town on a rail for daring to observe such.)
Is that worth turning into a whole grievance book, or is it enough to just say that..... Somebody has to go first, and there will be some discomfort until it becomes a normal thing.
2. In some ways, the book is just not honest
¶(p.65): Berkeley's tripling undergraduate tuition was not a result of cuts and state funding, but a result of the fact that education is inherently inflationary because it's not subject to market forces. (It was mentioned in the book that Celera sequenced genome for 1/10 the price of laboratories--at a faster rate.)
¶Yes, it is possible to write a book about someone somewhere who just happened to be researching something interesting that was later brought to commercial fruition.
But, in reality, the OVERWHELMING MAJORITY-->99%-- of (scientific) research will be of no impact. (I don't think anyone cares about Organofluorine Chemistry, although it was once a hot area.)
¶These people easily flying from one dream academic job to another and one postdoc to another just is not representative of reality for the heavy majority of people. (See article: "The Mathematics of the PHD Glut.")
¶(p.139) It is not that the advances by Doudna were created ex-nihilo. There were other research teams that were working on similar projects, and CRISPR-Cas9 had been described before, though the enzymes not actually isolated. It is clear that Doudna wanted to publish her research, lest she get "scooped." (p.202) At one point (January 2013), five papers on the same topic were all published in a single day.
¶¶(p.294) "China has one of the world's most controlled societies, and few things happen in clinics without the government's knowledge"
Just .....no.
Chinese people have been finding ways to get around and obstructive government for several thousand years by now. The reality on the ground is not quite the same as official pronouncements.
3. In some ways, the book is not useful/informative.
¶I have been to undergraduate/graduate school and worked in the science lab, and I do know that academics start the ideas and venture capitalists bring them to fruition.
And it would have to be that way, because people who are academics are categorically not the type of people used to finding ways to turn a profit. (And that's no surprise, if you look at the circumstances in any academic institution.)
¶It is well known that a lot of research projects that ultimately bear fruit are happenstance; this group just happens to have one person that knows somebody that specializes in x-ray crystallography of biomolecules.
Second order thoughts:
1. Sure does seem like wherever happening things ARE, black people ARE NOT. The author states as much (p.461) : "But there were very few African americans, either at the conference or on the benches in the various labs I had visited. In that regard, the new life sciences revolution resembles, unfortunately, the digital revolution. If there are not efforts at outreach and mentorship, biotechnology will be yet another revolution that leaves most blacks behind."
And it is true that I think there was only one black person pictured in this book, and all of the biotech companies were started up by Jewish/Chinese/White/ Indian (p.428)/ Arab (p.426)/Armenians (p.442)/ Turks (p.441)
2. I have lots of questions about how correct it is for researchers to leverage state-funded research into companies from which they take all the profits (Ch 28: there are no less than four companies started) It's like double dipping: taxpayers fund glorified government jobs (universities) and then the best ones take all of the profits. Isaacson lets slip the example of Stanford making $225 million by granting biotech licensees to companies (p.232).
3. If you are looking for a realistic picture of academic life for the great majority who manage to even make it there, you will not find it here. (No discussion of the one body problem, nor the two body problem. Nor endless post docs.)
4. Cultural backgrounds of the participants play a big role in the way that these events played out.
-Feng Zhang/ He Jiankui are far from unusual: It is just the Chinese Way to treat information as something that needs to be hoarded and to smile in your face charmingly, and leave out as much information as possible. It would have been a surprise if he didn't try to double cross / outfox his competitors.)
-Charpentier is hardly unique:It is a common thing in places like France and Italy for people to make an entire career bouncing from one postdoc to another (because there are no full-time positions available).
5. There's a lot of discussion about what is patentable, and who can bring what to market. But, apparently there are things such as "biohackers." By making genetic technology easier to handle, it also means that there are more people who will sell people what they want to buy - - even if it may be a bit dubious.
These discoveries can also be easily turned into biological weapons, and so there's that.
6. This book unintentionally ends up being an extension on Hayek's "The Fatal Conceit": governments don't have the power to ban the invention of technology, and only limited power to decide where it goes.
And let us be clear that money will decide where this goes.
7. The case has been made that the cure to genetic engineering capability is more genetic engineering capability because scale effects can lower the cost.
8. If ethicists and bioengineers are worried about not crossing a red line, fear not: It seems like the ONE red line that nobody is willing to cross is to make a connection between race and IQ. James Watson said out loud what everybody already knows, and he lost his position as Chancellor of Cold Spring Harbor and was banished from almost everything else.
9. "Eugenics" is a word that gives people all heated up, and is guaranteed to turn any discussion into Reduction ad Hitlerium. But, with the big business of bioengineering: you can just get ready for it.
And people who have more money will be able to take advantage of it much faster than everybody else.
*******
Synopses:
€€Part I (3-70): A scientist starts out interested in high school, and then she completes a PhD. She's able to make strides in the field (Molecular Biology / Genetics) because she chooses to not go into an oversubscribed area. (DNA vs. RNA).
€€Part II (71-152)): Introduction to "clustered regularly interspaced short palindromic repeats." (CRISPR).
Lots of Sturm und drang about one research group trying to scoop another, and ultimately the beginnings of a tool for gene editing.
€€Part III (153-244):
Gene editing at this point was not new, but unreliable / dangerous. A very lengthy blow by blow description (including personality profiles) of a bunch of scientists trying to scoop one the other to publish information that was discoverable just as a matter of time. Of course, there is lots of academic bickering about who discovered what. Finally, this culminated in a patent lawsuit that dragged on for probably about 8 years.
€€Part IV (245-266):
A brief chapter, deals with therapeutic applications. At this moment, the treatments are cost prohibitive. Something like $1 million per patient. Although, treatments of sickle cell have led to heritable changes.
€€Part V (267-298):
A brief history of the scenarios that involved scientists coming up with agreements as to what should and should not be done as well as what can and cannot be done. Apparently, the American attitude toward genetic engineering was one of great enthusiasm, whereas the Europeans came up with Oviedo Convention ("GMO" is a bad word in Europe--Germany and Britain excepted, for some reason.
€€Part VI(299-334) The first genetically modified babies are made by a Dissolute Mainland Chinese--He Jiamkui.
He thought that he would be a national hero in China, and what he got for his trouble was actually: i)a 3-year prison sentence; ii) $430,000 fine; iii) a lifetime ban from working in reproductive science. All were imposed by the Chinese government.) At this point, the germline is no longer a red line.
€€Part VII (335-370) More moral speculation and thought experiments. The difference between treatment (let's imagine treatment for Huntington's disease) versus enhancement (let's imagine making someone taller). The difference between absolute improvement and a positional improvement. Mood disorders are also associated with creativity. So, if you find a way to engineer them out of existence, what does that mean?
€€Part VIII (371-400) Odds and ends. The author goes into a lab and does an experiment that undergraduates have been able to do for the last 30 years. He revisits James Watson, who was punished for crossing the Red Line of linking race and IQ distributions
€€Part IX (401-477) Covid! Dealing with obstructive bureaucracy, such as the FDA and CDC. (Drugs and tests are regularly finished years before the FDA approves them. Covid created some limited fast-tracking, but the problem still exists.) Dealing with idiot politicians, such as Anthony Fauci. Still more bio companies started by US academics to solve problems that the state bureaucracy cannot.
Factoids:
1. It cost $3 billion to sequence human DNA the first time around.
2. Recombinant DNA was figured out in the early 70s. (By the time I was an undergraduate in the late 90s, it was an experiment that college sophomores could do.)
3. (p.99) Before recombinant DNA, 1 lb of insulin required 8,000 lb of pancreas ripped from 23,000 pigs/ cows.
4. What is the Difference Between CRISPR and Restriction Enzymes? CRISPR-Cas system is a prokaryotic immune system that confers resistance to foreign genetic elements. On the other hand, restriction enzymes are endonucleases that recognize a specific sequence of nucleotides and produce a double-stranded cut in the DNA
5. (ZFN) Zinc-finger nucleases are artificial restriction enzymes generated by fusing a zinc finger DNA-binding domain to a DNA-cleavage domain
6. TALENs are artificial restriction enzymes and can cut DNA strands at any desired sequence.
7. Three companies featured here: CRISPR Therapeutics; Editas Medicine; Intellia Therapeutics.
--2021 respective revenue ($millions): 910, 25.5, 33.1.
--Market cap ($billions): 3.97, 0.66, 3.32
--Net operating ($millions): 371, -192, -267
8. "Biohackers" are a thing. Enter the non-binary freak "Jo(siah) Zayner," stage left.
9. Germline and somatic cells are two different things. The first being what will be inherited and present for all times in the second being cells that exist as of a particular moment for some specified and limited use.
10. The major four infectious agents are: viruses, bacteria, fungi, protozoa.
11. Viral vaccines are of a few types. An attenuated version of the virus. Or a "killed" virus. Or a subunit of the live virus. Covid brought to the fore genetically engineered viruses.
Memorable quote (p.241): "Don't fight over divvying up the proceeds until you finish robbing the stagecoach."
*******
Verdict: I don't know if I recommend this book all that much. If you wanted an idea of the workings of DNA, better that you would read "The Gene" by Siddhartha Mukherjee.
The point of this book is about CRISPRs, and I would say it's probably better to search for another popular book without all of the literary spinach that is contained in this one.