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A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution
Goodreads Choice Award
Nominee for Best Science & Technology (2017)Two scientists explore the potential of a revolutionary genetics technology capable of easily and affordably manipulating DNA in human embryos to prevent specific diseases, addressing key concerns about related ethical and societal repercussions.
304 pages, Hardcover
First published June 13, 2017
About the author
Jennifer A. Doudna
11 books172 followersJennifer Anne Doudna is an American biochemist.
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December 28, 2019
One of the essential key technologies for the future of humanity
The previous methods before CRISPR were also not exactly precision instruments. Be it the use of radioactivity or toxicity, the gene gun, PCR, TALEN, CNF or genome editing. The susceptibility for errors was different, but in principle, the researchers always played to a part the crazy scientist who created new life. The critical difference is that a cheap mass application is possible with CRISPR.
Imagine a biotech toy box for children, with which they can tinker their cuddly pets or lethal viruses. It no longer seems too utopian. Also, the even more unrestricted contamination of nature is thus open to the flood of new life. One should imagine what comes together in a sewer system or the deltas of rivers in the long run. After all, the underlying method is based on an adaptive antiviral defense mechanism of bacteria. Moreover, we will integrate it everywhere possible what could have funny or tragic consequences.
The risk must be considered realistic. What is going to happen in the worst case, especially in face of and concerning exploitation and destruction of nature that could be reduced? In comparison, a genetically modified super invader is almost nothing. Much more attention is paid to the dangers of genetic engineering than to the destruction of the environment but what is despicable and exploitative is the patenting of life forms and the current misuse of technology by various biotech, pharmaceutical, agricultural and seed companies. They monopolize the plants and animals, which still actually belong to everyone.
The long-term consequences and contamination of the environment are not taken into account which causes in the US, among other things, that the non-genetically modified species go extinct. Because the pimped super vegetables supplant the natural competitors by two methods. On the one hand, the hybrid plants are immune to the various agricultural chemicals and furthermore, they mix more and more in the gene pool and there are fewer and fewer original plants left. The wild species die or are so profoundly contaminated that there is no unmodified genetic material left.
The same thing happens with pets and livestock. The best and most cute animals are genetically modified and the not so good, tasty or less cuddly species are becoming less or more contaminated sooner or later. If the last wild animals disappear, an original species is extinct.
In insects, as in the various extermination concepts for mosquitoes, when genetically modified organisms are released as extermination tools, this can trigger unimagined chain reactions. However, the legitimacy of this argument is difficult because of the victims of mosquito-borne diseases. A worst-case scenario would be to eradicate the disease carriers using Gene Drive and other methods. However, after a short cheer, it turns out that without them, the entire food chain collapses and it comes to famine.
Like all technologies, genetic engineering can be used responsibly or abused without restraint and drawing the line is complicated.
Genetic change is evolution and nature has always used genetic engineering. Viruses have been using genetic engineering inside us for millions of years, manipulating our DNA to make themselves immortal. How many of our bodily functions and reproductive possibilities are adaptations of viruses and other microorganisms can not yet be quantified. One knows too little about it.
The door to arbitrariness, greed for profit and omnipotence fantasies of the man about nature should not be opened. However, pure conservatism and undifferentiated hostility against science are as bad. They may sometimes appear hypocritical as altruistic commitment and conservation but on the contrary, they are similar, antiquated vehicles like optimizing the use of every natural resource. One has to balance the optimistic and pessimistic models of explanation against each other.
Indeed, various nemesis could be bred, and irreversible interference with nature could be caused when the organisms mess things up in the ecosystem. But one can also fix it with the same methods that caused the damage and without genetic engineering tools, many natural spaces may be lost forever.
On the positive side, nothing less than the solution to many human problems is within reach. Be it the path to immortality, the cure of many illnesses, the help against world hunger, the adaptation of people to space, neuro-enhancement, prevention of the outbreak of hereditary diseases, etc.
What is often forgotten in the public debate is the economic use of microorganisms. You can do pretty much anything with it, from renewable resources to various raw materials for industry and food. Bioreactors as part of energy self-sufficient, giant greenhouses and fish and insect breeding facilities in major cities.
The author represents a realistic and wise view of the moral obligations that must be borne by technology.
Unfortunately, not all humans do that. One question is whether ethical policy debates in such dimensions have a right to exist or are not prior unethical when it comes to saving the lives of millions and improving the lives of billions. A sharp and purely scientific calculation with hard facts is appropriate and not fundamental, philosophical debates about artifacts, such as the limitations of human empowerment to intervene in natural processes. The strange thing is that even in this dimension sex is the stimulus word. If, for millennia, only plants and animals are bred and genetically modified for decades, that does not matter. Fauna and flora are massively affected by crossbreeding hybrids, but as long as it doesn´t get nasty and filthy, nobody cares.
If, on the other hand, a fetus at a very early stage, or even just an ovum, is slightly pimped, there is resentment. Real dying people are not mentioned and unconscious eggs and sperm seem to have more rights than people in developing countries and the impoverished population in the countries of the egg and sperm owners. Outdated beliefs also play a role here. However, delaying the future and playing ethics seminar because of these anachronisms, is perverse.
The attitude of certain institutions also plays a role here. They have already made a name for themselves in preventing the availability of contraception to reduce unwanted pregnancies and diseases.
It is like being against the fire because you can burn yourself or cause a forest fire. Also, so to prefer to chew around for hours on raw meat and complain about the negligent querulants from the other cave, which maintain a permanent fire. This glaring light of knowledge and progress is undoubtedly bad for the eyes and brains of the hairy little humanoid apes.
A wiki walk can be as refreshing to the mind as a walk through nature in this completely overrated real-life outside books:
https://en.wikipedia.org/wiki/Genetic...
https://en.wikipedia.org/wiki/CRISPR
The previous methods before CRISPR were also not exactly precision instruments. Be it the use of radioactivity or toxicity, the gene gun, PCR, TALEN, CNF or genome editing. The susceptibility for errors was different, but in principle, the researchers always played to a part the crazy scientist who created new life. The critical difference is that a cheap mass application is possible with CRISPR.
Imagine a biotech toy box for children, with which they can tinker their cuddly pets or lethal viruses. It no longer seems too utopian. Also, the even more unrestricted contamination of nature is thus open to the flood of new life. One should imagine what comes together in a sewer system or the deltas of rivers in the long run. After all, the underlying method is based on an adaptive antiviral defense mechanism of bacteria. Moreover, we will integrate it everywhere possible what could have funny or tragic consequences.
The risk must be considered realistic. What is going to happen in the worst case, especially in face of and concerning exploitation and destruction of nature that could be reduced? In comparison, a genetically modified super invader is almost nothing. Much more attention is paid to the dangers of genetic engineering than to the destruction of the environment but what is despicable and exploitative is the patenting of life forms and the current misuse of technology by various biotech, pharmaceutical, agricultural and seed companies. They monopolize the plants and animals, which still actually belong to everyone.
The long-term consequences and contamination of the environment are not taken into account which causes in the US, among other things, that the non-genetically modified species go extinct. Because the pimped super vegetables supplant the natural competitors by two methods. On the one hand, the hybrid plants are immune to the various agricultural chemicals and furthermore, they mix more and more in the gene pool and there are fewer and fewer original plants left. The wild species die or are so profoundly contaminated that there is no unmodified genetic material left.
The same thing happens with pets and livestock. The best and most cute animals are genetically modified and the not so good, tasty or less cuddly species are becoming less or more contaminated sooner or later. If the last wild animals disappear, an original species is extinct.
In insects, as in the various extermination concepts for mosquitoes, when genetically modified organisms are released as extermination tools, this can trigger unimagined chain reactions. However, the legitimacy of this argument is difficult because of the victims of mosquito-borne diseases. A worst-case scenario would be to eradicate the disease carriers using Gene Drive and other methods. However, after a short cheer, it turns out that without them, the entire food chain collapses and it comes to famine.
Like all technologies, genetic engineering can be used responsibly or abused without restraint and drawing the line is complicated.
Genetic change is evolution and nature has always used genetic engineering. Viruses have been using genetic engineering inside us for millions of years, manipulating our DNA to make themselves immortal. How many of our bodily functions and reproductive possibilities are adaptations of viruses and other microorganisms can not yet be quantified. One knows too little about it.
The door to arbitrariness, greed for profit and omnipotence fantasies of the man about nature should not be opened. However, pure conservatism and undifferentiated hostility against science are as bad. They may sometimes appear hypocritical as altruistic commitment and conservation but on the contrary, they are similar, antiquated vehicles like optimizing the use of every natural resource. One has to balance the optimistic and pessimistic models of explanation against each other.
Indeed, various nemesis could be bred, and irreversible interference with nature could be caused when the organisms mess things up in the ecosystem. But one can also fix it with the same methods that caused the damage and without genetic engineering tools, many natural spaces may be lost forever.
On the positive side, nothing less than the solution to many human problems is within reach. Be it the path to immortality, the cure of many illnesses, the help against world hunger, the adaptation of people to space, neuro-enhancement, prevention of the outbreak of hereditary diseases, etc.
What is often forgotten in the public debate is the economic use of microorganisms. You can do pretty much anything with it, from renewable resources to various raw materials for industry and food. Bioreactors as part of energy self-sufficient, giant greenhouses and fish and insect breeding facilities in major cities.
The author represents a realistic and wise view of the moral obligations that must be borne by technology.
Unfortunately, not all humans do that. One question is whether ethical policy debates in such dimensions have a right to exist or are not prior unethical when it comes to saving the lives of millions and improving the lives of billions. A sharp and purely scientific calculation with hard facts is appropriate and not fundamental, philosophical debates about artifacts, such as the limitations of human empowerment to intervene in natural processes. The strange thing is that even in this dimension sex is the stimulus word. If, for millennia, only plants and animals are bred and genetically modified for decades, that does not matter. Fauna and flora are massively affected by crossbreeding hybrids, but as long as it doesn´t get nasty and filthy, nobody cares.
If, on the other hand, a fetus at a very early stage, or even just an ovum, is slightly pimped, there is resentment. Real dying people are not mentioned and unconscious eggs and sperm seem to have more rights than people in developing countries and the impoverished population in the countries of the egg and sperm owners. Outdated beliefs also play a role here. However, delaying the future and playing ethics seminar because of these anachronisms, is perverse.
The attitude of certain institutions also plays a role here. They have already made a name for themselves in preventing the availability of contraception to reduce unwanted pregnancies and diseases.
It is like being against the fire because you can burn yourself or cause a forest fire. Also, so to prefer to chew around for hours on raw meat and complain about the negligent querulants from the other cave, which maintain a permanent fire. This glaring light of knowledge and progress is undoubtedly bad for the eyes and brains of the hairy little humanoid apes.
A wiki walk can be as refreshing to the mind as a walk through nature in this completely overrated real-life outside books:
https://en.wikipedia.org/wiki/Genetic...
https://en.wikipedia.org/wiki/CRISPR
February 7, 2024
On October 22nd 2019 an article ran in The Guardian announcing the first birthdays of twin girls. What made them special is that they are the first humans to be born from gene edited embryos, the first reported case of humans determining their own evolution. The girls’ genes were modified to make them resistant to HIV. Their children will be able to inherit the same trait. The gene edit may make them more susceptible to other diseases such as West Nile virus. How many other ways this may affect the girls is not known. Performed in China with the parent’s approval, this first instance of gene modification of the human germline will be just the beginning. We are entering the era of designer babies. The tool used is known as CRISPR-Cas9. Its advent has bestowed a new level of precision in gene editing and made the technique readily available for widespread use. The story of CRISPR and its impact is the subject of Doudna’s book.
Doudna is a biochemist who spent years running a lab at the forefront of CRISPR research. CRISPR is derived from bacteria that use a package of enzymes and RNA to disable viral phages by cutting out a piece of their DNA. Over the past decade Doudna’s lab and others tinkered with the native bacterial package turning it into a tool that can cut and replace any desired segment of DNA in a cell. CRISPR-Cas9 has two basic parts, a guide RNA sequence that mimics the target DNA and a DNA cutting enzyme. The RNA finds and matches up with the DNA target signaling Cas9 to cut out the indicated strand. To disable a gene that is all that is needed. To replace it an RNA template is provided to the cell to use in its repair of the cut. For example in sickle cell disease one sole DNA letter is at fault. To change it the template would substitute the correct letter. CRISPR can also be used to replace longer DNA sequences and multiple sequences.
CRISPR while a huge improvement over prior techniques has some limitations with delivery and accuracy. Sometimes an untargeted DNA sequence can be changed and targeted sequences can be missed. But since Doudna’s book was published two years ago, there have been significant enhancements to the technology. One that increases accuracy is called prime editing. With so many scientists focused on CRISPR, It can’t be many years before a future version operates as reliably as the find and replace feature on your computer. Delivery of the CRISPR package to somatic cells in vivo (in a living organism) can be difficult. As with prior gene therapies an agent such as a virus must target and insert CRISPR in the intended cells. However, there has been success doing this in animal models. Delivery ex vivo such as editing T cells to fight blood cancers is much easier. Delivery to a single cell embryo that has been fertilized in vitro is quite easy. Afterwards the embryo can be examined to verify the proper edit has been made before it is implanted.
Doudna divides her book into two sections. The first part is about the discovery of CRISPR and the refinement of it into a useful gene editor. The second part covers what CRISPR can do and the concerns that accompany those applications. She gives us a little history of gene editing and goes into how she got involved and the work her lab did to make CRISPR a more reliable product. In the telling we learn some science that is nicely presented in an accessible way. The telling of the story is delivered in the first person and Doudna herself is at the center of it. Many sentences begin with “I”. I felt the many personal asides and antidotes were distracting. Other readers may like the personal touch.
The second section deals with Doudna’s realization that she has helped unleash a product that can be misused in catastrophic ways. She references Oppenheimer as an example of her own tormented mind. Both scientists were driven to accomplish their goal. Afterward they considered the consequences and how those made them feel. There is a tremendous amount of good that CRISPR and its successors can accomplish from basic research to improving crops and farm animals for better yields and nutrition to fixing and preventing many diseases such as cystic fibrosis, Huntington’s, HIV, hemophilia and Duchenne muscular dystrophy to name just a few. There will certainly be great demand from families affected by these terrible diseases. There will also be demand not just to eliminate disease but to alter physical appearance and other attributes. It is important to consider that when the fixes are in the human germline, they perpetuate in all following generations. Gene functions are complex and intertwined. Changing them can lead to unintended consequences.
In my view, unlike Huxley’s Brave New World we won’t have to wait until the year 2540 for gene editing technology to change the world, 2054 is more like it. If rich parents see no problem spending vast sums to put their children in a choice college, what will they spend to make sure their children (and grandchildren) are smart, beautiful, athletic, etc? Doudna proposes approaching the problem in traditional ways with conferences, international agreements, guidelines, laws where they can be passed, making the public aware, etc. But the genie is out of the bottle and if what we have seen from the stem cell industry is any indication, I would expect the gene editing business to pop up worldwide. Just like the stem cell clinics that now litter the globe offering untested treatments, clinics offering CRISPR technology will be fraught with danger though much of it may not be evident for generations.
Doudna mentions that her co-author, Sam Sternberg, had already been interviewed by a startup that would offer clients a “CRISPR baby.” She notes, “…an aspiring scientist with the most basic training can accomplish feats that would have been inconceivable just a few years ago.” Sophisticated software is readily available to identify gene sequences for targeting. Doudna adds that some experts say “…with today’s tools, anyone can set up a CRISPR lab for just $2,000.” Do it yourself kits are selling for $130. She wonders if we could see a modern day reprise of the eugenics movement.
We should be aware of a technology called “gene drive”. This is the placement of new genes in with existing “selfish genes” which means that more than the normal 50% of offspring inherit the new traits. Such placement ensures rapid spread through a population. CRISPR is the perfect tool to accomplish this. Also CRISPR itself can be placed in the genome along with a genetic payload, which would then be copied to other chromosomes and spread throughout the genome. Gene drives have been proposed to eradicate mosquitoes by spreading recessive sterilization genes through the population until it would collapse. DARPA has invested $100 million and the Gates Foundation $75 million on research into this. Gene drives are a potentially dangerous technology that could have unforeseen environmental consequences. Gene drives could also be militarized targeting food sources or even microbes in the human microbiome. These applications have been referred to as “gene bombs”.
Doudna clearly sees the danger and she spends chapters lamenting over it. While I found her angst and bad dreams a bit much, her points are all well taken. The title of The Guardian article referenced above, “Gene editing like Crispr is too important to be left to scientists alone,” sums it up. I highly recommend this book for those unfamiliar with the topic. It’s timely, important and accessible.
Doudna is a biochemist who spent years running a lab at the forefront of CRISPR research. CRISPR is derived from bacteria that use a package of enzymes and RNA to disable viral phages by cutting out a piece of their DNA. Over the past decade Doudna’s lab and others tinkered with the native bacterial package turning it into a tool that can cut and replace any desired segment of DNA in a cell. CRISPR-Cas9 has two basic parts, a guide RNA sequence that mimics the target DNA and a DNA cutting enzyme. The RNA finds and matches up with the DNA target signaling Cas9 to cut out the indicated strand. To disable a gene that is all that is needed. To replace it an RNA template is provided to the cell to use in its repair of the cut. For example in sickle cell disease one sole DNA letter is at fault. To change it the template would substitute the correct letter. CRISPR can also be used to replace longer DNA sequences and multiple sequences.
CRISPR while a huge improvement over prior techniques has some limitations with delivery and accuracy. Sometimes an untargeted DNA sequence can be changed and targeted sequences can be missed. But since Doudna’s book was published two years ago, there have been significant enhancements to the technology. One that increases accuracy is called prime editing. With so many scientists focused on CRISPR, It can’t be many years before a future version operates as reliably as the find and replace feature on your computer. Delivery of the CRISPR package to somatic cells in vivo (in a living organism) can be difficult. As with prior gene therapies an agent such as a virus must target and insert CRISPR in the intended cells. However, there has been success doing this in animal models. Delivery ex vivo such as editing T cells to fight blood cancers is much easier. Delivery to a single cell embryo that has been fertilized in vitro is quite easy. Afterwards the embryo can be examined to verify the proper edit has been made before it is implanted.
Doudna divides her book into two sections. The first part is about the discovery of CRISPR and the refinement of it into a useful gene editor. The second part covers what CRISPR can do and the concerns that accompany those applications. She gives us a little history of gene editing and goes into how she got involved and the work her lab did to make CRISPR a more reliable product. In the telling we learn some science that is nicely presented in an accessible way. The telling of the story is delivered in the first person and Doudna herself is at the center of it. Many sentences begin with “I”. I felt the many personal asides and antidotes were distracting. Other readers may like the personal touch.
The second section deals with Doudna’s realization that she has helped unleash a product that can be misused in catastrophic ways. She references Oppenheimer as an example of her own tormented mind. Both scientists were driven to accomplish their goal. Afterward they considered the consequences and how those made them feel. There is a tremendous amount of good that CRISPR and its successors can accomplish from basic research to improving crops and farm animals for better yields and nutrition to fixing and preventing many diseases such as cystic fibrosis, Huntington’s, HIV, hemophilia and Duchenne muscular dystrophy to name just a few. There will certainly be great demand from families affected by these terrible diseases. There will also be demand not just to eliminate disease but to alter physical appearance and other attributes. It is important to consider that when the fixes are in the human germline, they perpetuate in all following generations. Gene functions are complex and intertwined. Changing them can lead to unintended consequences.
In my view, unlike Huxley’s Brave New World we won’t have to wait until the year 2540 for gene editing technology to change the world, 2054 is more like it. If rich parents see no problem spending vast sums to put their children in a choice college, what will they spend to make sure their children (and grandchildren) are smart, beautiful, athletic, etc? Doudna proposes approaching the problem in traditional ways with conferences, international agreements, guidelines, laws where they can be passed, making the public aware, etc. But the genie is out of the bottle and if what we have seen from the stem cell industry is any indication, I would expect the gene editing business to pop up worldwide. Just like the stem cell clinics that now litter the globe offering untested treatments, clinics offering CRISPR technology will be fraught with danger though much of it may not be evident for generations.
Doudna mentions that her co-author, Sam Sternberg, had already been interviewed by a startup that would offer clients a “CRISPR baby.” She notes, “…an aspiring scientist with the most basic training can accomplish feats that would have been inconceivable just a few years ago.” Sophisticated software is readily available to identify gene sequences for targeting. Doudna adds that some experts say “…with today’s tools, anyone can set up a CRISPR lab for just $2,000.” Do it yourself kits are selling for $130. She wonders if we could see a modern day reprise of the eugenics movement.
We should be aware of a technology called “gene drive”. This is the placement of new genes in with existing “selfish genes” which means that more than the normal 50% of offspring inherit the new traits. Such placement ensures rapid spread through a population. CRISPR is the perfect tool to accomplish this. Also CRISPR itself can be placed in the genome along with a genetic payload, which would then be copied to other chromosomes and spread throughout the genome. Gene drives have been proposed to eradicate mosquitoes by spreading recessive sterilization genes through the population until it would collapse. DARPA has invested $100 million and the Gates Foundation $75 million on research into this. Gene drives are a potentially dangerous technology that could have unforeseen environmental consequences. Gene drives could also be militarized targeting food sources or even microbes in the human microbiome. These applications have been referred to as “gene bombs”.
Doudna clearly sees the danger and she spends chapters lamenting over it. While I found her angst and bad dreams a bit much, her points are all well taken. The title of The Guardian article referenced above, “Gene editing like Crispr is too important to be left to scientists alone,” sums it up. I highly recommend this book for those unfamiliar with the topic. It’s timely, important and accessible.
October 29, 2022
This book's coauthor, Jennifer Doudna, together with Emmanuelle Charpentier published a seminal 2012 paper that demonstrated that CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) could be used for programmable gene editing. The whole field of CRISPR has since become the hottest focus of biological research because its use now provides a relatively low cost and simple way to make precise changes to the double helix DNA strand.
This book is written in the first person voice of Doudna and first tells of her academic training and how she came to learn about CRSPR. Then the book provides a short history of the development of gene splicing techniques. Various methods of gene targeting and splicing had been developed (TALEN and ZFNs) prior to the discovery of CRISPR, but they were difficult and expensive procedures.
The book then reviews possible future applications of CRSPR in congenital and infectious diseases (cure MD and prevent AIDS), medicine (immunological targeting of cancer cells), surgery (growing human compatible organs for implantation), zoology (bring back the wooly mammoth), entomology (get rid of mosquitos), and agriculture (disease resistant super crops). Science is in the early stages of research that will bring these applications into popular use, but it seems that almost anything imaginable may be possible. The applications listed above within parenthesis are examples selected from the many discussed by this book.
The book also describes various possible means of delivery. It also discusses the difference between making changes outside (in vitro) versus introduction of change agents directly to a living body.
Toward the end of the book Doudna discusses her role in organizing the first conferences to discuss the ethics of making changes that will be inherited by future generations (a.k.a germ-line modification). Humans now can influence the future evolution of species, including humans.
The discussion of possible future changes that might be desired by humans beyond the eradication of congenital diseases can lead to unexpected possibilities. One hilarious possibility that caught my eye was the ability of reduce underarm odor (a known simple change to the DNA is known to make a difference).
The history of the discovery of CRISPR reminded me of the following quotation:
What was so strange about CRISPR is that it appears in all biological families including Archaea which means the pattern developed extremely early in evolution. Its persistence and prevalence must mean that it is essential for life, but in the early years after its discovery its possible purpose was a mystery. It even had been thought of as "junk" DNA since it seemed to serve no purpose.
Another "aha moment" came in the early 2000s when a Danish yogurt manufacturer noticed that their bacterial yogurt cultures were able to steal bits of DNA from attacking viruses and then use that information to create bacteriophages to make themselves immune from attack. CRISPR appeared to be used in finding the locations on the DNA strand to be changed. It was this and other papers at this time that alerted the research community to the fact that CRISPR appeared to be nature's own method of making gene edits at precise locations.
It can be argued that the possibility of controlling biological evolution may prove to be the most significant scientific breakthrough ever made toward the relief of human suffering. Of course, there may be unintended consequences.
The following link is to an article about UC Berkeley's lawsuit challenging MIT's Broad Institute's CRISPR patent:
https://www.theverge.com/2017/4/13/15...
This book is written in the first person voice of Doudna and first tells of her academic training and how she came to learn about CRSPR. Then the book provides a short history of the development of gene splicing techniques. Various methods of gene targeting and splicing had been developed (TALEN and ZFNs) prior to the discovery of CRISPR, but they were difficult and expensive procedures.
The book then reviews possible future applications of CRSPR in congenital and infectious diseases (cure MD and prevent AIDS), medicine (immunological targeting of cancer cells), surgery (growing human compatible organs for implantation), zoology (bring back the wooly mammoth), entomology (get rid of mosquitos), and agriculture (disease resistant super crops). Science is in the early stages of research that will bring these applications into popular use, but it seems that almost anything imaginable may be possible. The applications listed above within parenthesis are examples selected from the many discussed by this book.
The book also describes various possible means of delivery. It also discusses the difference between making changes outside (in vitro) versus introduction of change agents directly to a living body.
Toward the end of the book Doudna discusses her role in organizing the first conferences to discuss the ethics of making changes that will be inherited by future generations (a.k.a germ-line modification). Humans now can influence the future evolution of species, including humans.
The discussion of possible future changes that might be desired by humans beyond the eradication of congenital diseases can lead to unexpected possibilities. One hilarious possibility that caught my eye was the ability of reduce underarm odor (a known simple change to the DNA is known to make a difference).
The history of the discovery of CRISPR reminded me of the following quotation:
The most exciting phrase to hear in science, the one that heralds new discoveries, is not “Eureka!” (I found it!) butIt's my guess that the initial observations of the existence and biological use of CRISPR may have included a version of the above quotation.
“That’s funny …”
— Isaac Asimov
What was so strange about CRISPR is that it appears in all biological families including Archaea which means the pattern developed extremely early in evolution. Its persistence and prevalence must mean that it is essential for life, but in the early years after its discovery its possible purpose was a mystery. It even had been thought of as "junk" DNA since it seemed to serve no purpose.
Another "aha moment" came in the early 2000s when a Danish yogurt manufacturer noticed that their bacterial yogurt cultures were able to steal bits of DNA from attacking viruses and then use that information to create bacteriophages to make themselves immune from attack. CRISPR appeared to be used in finding the locations on the DNA strand to be changed. It was this and other papers at this time that alerted the research community to the fact that CRISPR appeared to be nature's own method of making gene edits at precise locations.
It can be argued that the possibility of controlling biological evolution may prove to be the most significant scientific breakthrough ever made toward the relief of human suffering. Of course, there may be unintended consequences.
The following link is to an article about UC Berkeley's lawsuit challenging MIT's Broad Institute's CRISPR patent:
https://www.theverge.com/2017/4/13/15...
June 18, 2018
This is a wonderful book, written by the scientist who discovered that the CRISPR reaction could be applied as a powerful gene-editing tool. In the first half of the book, Jennifer Doudna writes a powerful story about the history of gene manipulation and eventually, gene editing. With this technique, scientists can edit an individual DNA letter, replacing or inserting mutation or error in the DNA code. The first half of the book is very technical, and I cannot say that I followed it completely. The book is illustrated with numerous diagrams, but unfortunately, these diagrams did not shine much insight into the discussion. I am not really sure why they were included, at all.
The CRISPR reaction is a method that evolved in bacteria, to defend against invading viruses. Jennifer Doudna, in collaboration with other scientists, discovered how that very method could be used to edit genes with very high efficiency. Moreover, the method is relatively simply, and does not require an expensive laboratory.
The second half of the book is much less technical in nature. First, the book describes a number of successful uses of CRISPR, in the manipulation of genes in plants, animals, and even in humans. Then the book changes course somewhat, and describes the ethical dilemmas that await society, as we discover the capabilities and limitations of gene editing. These dilemmas will occur when attempts to edit the human genome are begun in earnest. What will be the unintended consequences? The techniques have the greatest promise in curing genetically inherited diseases, like sickle cell, Tay Sachs, some types of cancer, and many others. Right now, there is the possibility that CRISPR might edit no only the intended DNA sequence, but other DNA sequences as well. Perhaps in time, such problems will be overcome.
I just love books by scientists who have been at the forefront of research--provided that the books are well written. This book certainly qualifies, and I whole-heartedly recommend it to anybody who is interested in the new revolutionary advances in the forefront of science and medicine.
The CRISPR reaction is a method that evolved in bacteria, to defend against invading viruses. Jennifer Doudna, in collaboration with other scientists, discovered how that very method could be used to edit genes with very high efficiency. Moreover, the method is relatively simply, and does not require an expensive laboratory.
The second half of the book is much less technical in nature. First, the book describes a number of successful uses of CRISPR, in the manipulation of genes in plants, animals, and even in humans. Then the book changes course somewhat, and describes the ethical dilemmas that await society, as we discover the capabilities and limitations of gene editing. These dilemmas will occur when attempts to edit the human genome are begun in earnest. What will be the unintended consequences? The techniques have the greatest promise in curing genetically inherited diseases, like sickle cell, Tay Sachs, some types of cancer, and many others. Right now, there is the possibility that CRISPR might edit no only the intended DNA sequence, but other DNA sequences as well. Perhaps in time, such problems will be overcome.
I just love books by scientists who have been at the forefront of research--provided that the books are well written. This book certainly qualifies, and I whole-heartedly recommend it to anybody who is interested in the new revolutionary advances in the forefront of science and medicine.
May 3, 2019
Very similar to Watson's "The Double Helix", this book is a part story of discovery and part a textbook, in this case on the topic of CRISPR, from a scientist deeply and technically involved in the technology. The first half of the book explains the basics of DNA, the central dogma, the massive, ancient (and still ongoing) virus-bacteria molecular warfare, the historical context of gene editing research, and finally how CRISPR was discovered and why it is such a big deal.
CRISPR evolved as part of a bacterial immune system where the bacteria stores explicit records of viral DNA segments in their genome. Together with a number of Cas (CRISPR associated) proteins encoded by genes in the vicinity, the resulting molecular assembly is able to search the genome for stretches that "match", inducing a double stranded break that disables the gene. It's incredible that this molecular machine was found by evolution and that there are so many forms of it. It's hard to imagine the Cas9 protein whizzing about the nucleus in brownian motion (it does not hydrolize ATP!), interacting with chromatin/histones and somehow cutting up matches. The biophysics of this process elude me.
Anyway, this immune system mechanism can be repurposed, improved and generalized to perform very targeted and cheap gene editing (delete, insert, substitute, invert, ...), gene expression up/down regulation, tagging, etc. This is now actively utilized in animals and plants (in both somatic and germ cells), and also on humans (in somatic cells for treatment of many diseases, or more worryingly in the germ line for making permanent targeted changes to human DNA). The book also discusses gene drives, which allow us to hack evolution itself, e.g. giving us the ability to wipe out the entire population of mosquitos, on which I have very mixed opinions. It also goes into some remaining challenges such as specificity, delivery, etc. In some aspects it is not as comprehensive as I'd like (e.g. how the adaptation part works, or what the limits are).
In summary, this is really the beginning of a powerful set of technologies with broad societal implications, as we begin to reprogram both us and the nature around us in hyper-targeted ways. It's refreshing to find a book that does such a good job describing large portions of it without dumbing it down too much, and also doing a good job hinting at some of the associated ethical dilemmas ahead of us.
CRISPR evolved as part of a bacterial immune system where the bacteria stores explicit records of viral DNA segments in their genome. Together with a number of Cas (CRISPR associated) proteins encoded by genes in the vicinity, the resulting molecular assembly is able to search the genome for stretches that "match", inducing a double stranded break that disables the gene. It's incredible that this molecular machine was found by evolution and that there are so many forms of it. It's hard to imagine the Cas9 protein whizzing about the nucleus in brownian motion (it does not hydrolize ATP!), interacting with chromatin/histones and somehow cutting up matches. The biophysics of this process elude me.
Anyway, this immune system mechanism can be repurposed, improved and generalized to perform very targeted and cheap gene editing (delete, insert, substitute, invert, ...), gene expression up/down regulation, tagging, etc. This is now actively utilized in animals and plants (in both somatic and germ cells), and also on humans (in somatic cells for treatment of many diseases, or more worryingly in the germ line for making permanent targeted changes to human DNA). The book also discusses gene drives, which allow us to hack evolution itself, e.g. giving us the ability to wipe out the entire population of mosquitos, on which I have very mixed opinions. It also goes into some remaining challenges such as specificity, delivery, etc. In some aspects it is not as comprehensive as I'd like (e.g. how the adaptation part works, or what the limits are).
In summary, this is really the beginning of a powerful set of technologies with broad societal implications, as we begin to reprogram both us and the nature around us in hyper-targeted ways. It's refreshing to find a book that does such a good job describing large portions of it without dumbing it down too much, and also doing a good job hinting at some of the associated ethical dilemmas ahead of us.
June 26, 2017
Last time a book gave me this feeling of awe and amazement was reading Stephen Hawkin's "Brief history of time" 20 years ago. It speaks volumes to Jennifer's ability to distilled the essential on this complex topic that I left feeling I had a good grasp on the subject (albeit with my mind racing over a million questions). A must read.
January 30, 2024
This book does an excellent job of explaining the CRISPR-Cas9 gene editing technology in layman's terms. However, I thought it underdelivered on examining the future implications — both positive and negative — of its practical uses.
January 3, 2020
Excellent book, though the technical stuff takes some work, and perhaps some background in biochemistry, to follow completely. The review to read here in Max's, https://www.goodreads.com/review/show...
Why don’t you read his writeup first, while I write up my notes and do my homework? I’ll wait.
Biochemist Jennifer Doudna is one of the pioneers in gene-editing research. She and her colleagues discovered the CRISPR-Cas9 genome editing tool in 2012. The names are just chemical acronyms. You will learn more about them if you read the book, but the take-home here is that this discovery is a MUCH faster and cheaper way to edit (it seems) most DNA genomes of life on our planet. Editing a genome, which might have cost $25,000 using the best previously-available tool, could now be done for $50 or less. And in minutes vs. months! The New York Times called this "one of the most significant discoveries in the history of biology." My guess is, she will be in line for part of a Nobel Prize, not too far down the line. And her work is a fine reminder of the value of basic research, and scientific curiosity.
If you (like me) are a visual person, this animation is the place to start your understanding of the topic in about 4 minutes: "Genome Editing with CRISPR-Cas9",
https://www.youtube.com/watch?v=2pp17...
Most highly recommended!
This powerful new tool is still in its infancy, but it has such obvious potential that it has attracted many, many researchers worldwide. Plus commercial interests and patent disputes. So far, the most promising applications of gene editing include possible cures for genetic diseases (such as Huntington’s and many more?), improvements in crops (wheat, rice) and livestock (cattle, chickens). She briefly mentions the potential problems with getting these foods accepted by the general public, given the stormclouds over GMO foods. And the most controversial possible application is "improving" human kids. I am reminded of the ancient words of wisdom, “Be careful what you wish for.”
Two good professional reviews:
Public Library of Science (PLOS): https://blogs.plos.org/synbio/2018/03...
BioNews: https://www.bionews.org.uk/page_96144
Doudna’s 2015 TED talk, "How CRISPR lets us edit our DNA":
https://www.youtube.com/watch?v=TdBAH...
16 min, 2015. Good talk, but I can’t understand the moderator at the end!
Why don’t you read his writeup first, while I write up my notes and do my homework? I’ll wait.
Biochemist Jennifer Doudna is one of the pioneers in gene-editing research. She and her colleagues discovered the CRISPR-Cas9 genome editing tool in 2012. The names are just chemical acronyms. You will learn more about them if you read the book, but the take-home here is that this discovery is a MUCH faster and cheaper way to edit (it seems) most DNA genomes of life on our planet. Editing a genome, which might have cost $25,000 using the best previously-available tool, could now be done for $50 or less. And in minutes vs. months! The New York Times called this "one of the most significant discoveries in the history of biology." My guess is, she will be in line for part of a Nobel Prize, not too far down the line. And her work is a fine reminder of the value of basic research, and scientific curiosity.
If you (like me) are a visual person, this animation is the place to start your understanding of the topic in about 4 minutes: "Genome Editing with CRISPR-Cas9",
https://www.youtube.com/watch?v=2pp17...
Most highly recommended!
This powerful new tool is still in its infancy, but it has such obvious potential that it has attracted many, many researchers worldwide. Plus commercial interests and patent disputes. So far, the most promising applications of gene editing include possible cures for genetic diseases (such as Huntington’s and many more?), improvements in crops (wheat, rice) and livestock (cattle, chickens). She briefly mentions the potential problems with getting these foods accepted by the general public, given the stormclouds over GMO foods. And the most controversial possible application is "improving" human kids. I am reminded of the ancient words of wisdom, “Be careful what you wish for.”
Two good professional reviews:
Public Library of Science (PLOS): https://blogs.plos.org/synbio/2018/03...
BioNews: https://www.bionews.org.uk/page_96144
Doudna’s 2015 TED talk, "How CRISPR lets us edit our DNA":
https://www.youtube.com/watch?v=TdBAH...
16 min, 2015. Good talk, but I can’t understand the moderator at the end!
October 14, 2020
https://science.sciencemag.org/conten...
This was the ground breaking paper published by the author of this book along with other researchers that made way for a technology that has alarmed scientists with its potential, to the extent that comparisons with nuclear fission are ubiquitous. Being in an unrelated field of engineering, this scientific article was difficult to fully comprehend over the years since it was published, but having read this book I have found myself able to truly appreciate the incredible potential associated with this technology and exactly why it has scientists concerned across the globe.
If you are reading this review and are even lightly inclined towards science and can tolerate non-fiction, read this book. Public awareness about such topics and what they entail from a scientific perspective as soon as possible is the best way to avoid getting swept-up in the social media galore created by groups claiming things similar to 'evolution is wrong' or 'vaccines cause autism'. As an upside the book is also well written and goes into just enough details that most people should be able to understand it. Compared to this book there are bestselling thrillers that have invoked less of a thrill.
Update: October 2020, A well-deserved Nobel Prize in Chemistry to Emmanuelle Charpentier and Jennifer A. Doudna (https://www.sciencedaily.com/releases...)
This was the ground breaking paper published by the author of this book along with other researchers that made way for a technology that has alarmed scientists with its potential, to the extent that comparisons with nuclear fission are ubiquitous. Being in an unrelated field of engineering, this scientific article was difficult to fully comprehend over the years since it was published, but having read this book I have found myself able to truly appreciate the incredible potential associated with this technology and exactly why it has scientists concerned across the globe.
If you are reading this review and are even lightly inclined towards science and can tolerate non-fiction, read this book. Public awareness about such topics and what they entail from a scientific perspective as soon as possible is the best way to avoid getting swept-up in the social media galore created by groups claiming things similar to 'evolution is wrong' or 'vaccines cause autism'. As an upside the book is also well written and goes into just enough details that most people should be able to understand it. Compared to this book there are bestselling thrillers that have invoked less of a thrill.
Update: October 2020, A well-deserved Nobel Prize in Chemistry to Emmanuelle Charpentier and Jennifer A. Doudna (https://www.sciencedaily.com/releases...)
August 21, 2017
A great explanation of CRISPR Cas9 that recounts the research that uncovered it and makes a case for determining how we will responsibly control and wield this powerful tool in future gene editing. The ethical and moral questions are very difficult, and Doudna/Sternberg don't pretend to have solid answers, and instead encourage more discussion and, above all, communication because governments and society as a whole will have to drive policy (and they should do so in an informed way).
This was riveting all the way through. Incredibly timely and the sheer speed of this breakthrough is amazing and terrifying - adoption of CRISPR worldwide has pretty much outpaced discussions and policy-making. It's also very heartening to hear about scientists who deeply care about the repercussions of their work and will step out of their comfort zones (and labs) into the arena of policy and politics to get the conversation started.
I think this a must-read for people following genetics, but also for anyone interested in how science is truly global... and this is one real technology that in its implications and far-reaching consequences feels like science fiction.
This was riveting all the way through. Incredibly timely and the sheer speed of this breakthrough is amazing and terrifying - adoption of CRISPR worldwide has pretty much outpaced discussions and policy-making. It's also very heartening to hear about scientists who deeply care about the repercussions of their work and will step out of their comfort zones (and labs) into the arena of policy and politics to get the conversation started.
I think this a must-read for people following genetics, but also for anyone interested in how science is truly global... and this is one real technology that in its implications and far-reaching consequences feels like science fiction.
June 29, 2022
I won this book in a Goodreads giveaway! Definitely a subject I'd be interested in but maybe I wouldn't have pursued it otherwise, so thanks Goodreads.
Me being me, I found myself turned off by the personal element of the book. It's a good writing technique - it personalizes all the scientific information, which could be otherwise dry or hard to follow for some readers, and lends a natural timeline around which to structure the unfolding of the tale of CRISPR. So, objectively, very well done. Subjectively, I don't particularly want to hear about the story of anyone's life as it relates to and has been changed and affected by this technology. Why I am a curmudgeon like this, I do not know. But I guess the only legitimate complaint I could actually come up with is that the illustrations seemed pretty pointless and not very illuminating.
But other than that, I was fooled into thinking I had a pretty decent understanding of how CRISPR gene editing works and the surrounding fields in which it lays, which definitely speaks of clear science writing. And though I sort of fussed and fumed over Doudna's frequent laments of 'oh what have I wrought' throughout the book, she came together at the end with a beautifully measured summary of the relevant issues. The frequent laments served to put her on the side of the hand-wringers and others with concerns about the downsides of the use of this technology; starting from a point of disquiet she walked us through a calm and informed discussion about many many things to take into consideration, addressing common objections people might have with sensible responses - for example, pointing out that all new technologies, such as computers and cell phones, were once prohibitively expensive and thusly reserved for the rich, but this only enabled the technology to improve to the point of being affordable for everyone, rather than resulting in a technology gap between haves and have nots. She successfully exemplified everything she is hoping to have in a conversation about how to actually discuss a complex issue that consists largely of trade-offs. For this, I suppose I will forgive the slight hysteria of the title.
Me being me, I found myself turned off by the personal element of the book. It's a good writing technique - it personalizes all the scientific information, which could be otherwise dry or hard to follow for some readers, and lends a natural timeline around which to structure the unfolding of the tale of CRISPR. So, objectively, very well done. Subjectively, I don't particularly want to hear about the story of anyone's life as it relates to and has been changed and affected by this technology. Why I am a curmudgeon like this, I do not know. But I guess the only legitimate complaint I could actually come up with is that the illustrations seemed pretty pointless and not very illuminating.
But other than that, I was fooled into thinking I had a pretty decent understanding of how CRISPR gene editing works and the surrounding fields in which it lays, which definitely speaks of clear science writing. And though I sort of fussed and fumed over Doudna's frequent laments of 'oh what have I wrought' throughout the book, she came together at the end with a beautifully measured summary of the relevant issues. The frequent laments served to put her on the side of the hand-wringers and others with concerns about the downsides of the use of this technology; starting from a point of disquiet she walked us through a calm and informed discussion about many many things to take into consideration, addressing common objections people might have with sensible responses - for example, pointing out that all new technologies, such as computers and cell phones, were once prohibitively expensive and thusly reserved for the rich, but this only enabled the technology to improve to the point of being affordable for everyone, rather than resulting in a technology gap between haves and have nots. She successfully exemplified everything she is hoping to have in a conversation about how to actually discuss a complex issue that consists largely of trade-offs. For this, I suppose I will forgive the slight hysteria of the title.
February 22, 2022
At an Ethical Conference on Gene Editing an individual approached the brilliant doctor Jennifer A. Doudna and told her that he had three sisters at the moment suffering terribly from a genetic disease that would shortly take their lives. He could not understand how anybody who has ever seen someone suffering from such diseases could find anything wrong with the gene editing process that by simply changing a letter in one's DNA to match its opposite letter could put an end to so many dastardly genetic diseases.
The answer seems simple, at least to me, who like billions of other people have seen friends and relatives suffer and die from genetic diseases. Imagine a world where we could eliminate so many childhood cancers, cystic fibrosis, blindness, sickle cell anemia, HIV and God knows how many other diseases with a process that has come to be known as "CRISPR." CRISPR, a revolutionary technology that Dr. Doudna help create, and was awarded the Nobel Peace Prize in chemistry in 2020, that makes heritable changes in one's DNA that would make a genetic disease like sickle cell anemia never infect a person who was destined to suffer from the agonizing disorder.
Well, that technology has arrived and if you don't believe it just look up what the Moderna and Pfizer vaccines, that have proven so effective against the covid-19 virus, are made up of and which has cured cases of HIV and sickle cell anemia. What is so amazing, is how simple it really is according to Dr. Doudna and thousands of other scientists and researches.
But like the vaccines against Covid-19, there are many critics who say we should not mess around with the evolutionary process or that it's against God's will. I don't agree with them and the only real drawback to this amazing technology is the possibility that humans will use it to make 'better' offspring...more intelligent, muscular, and naturally more beautiful children.
Last year, I said the most important book I read was Walter Isaacson's "The Code Breaker," which was mostly about Dr. Doudna, the scientists, and researchers who have help create this technology. Mr. Isaacson's book definitely helped me understand Dr. Doudna and Dr. Sternberg's book, especially the first half that dealt with terms that would have been difficult to understand if I had not read Mr. Isaacson's book.
"A Crack in Creation," and the technology of CRISPR might seem unthinkable to many people, but for me it might very well be the most important scientific and medical discovery in many and many of years...if not the most important medical breakthrough in centuries.
The answer seems simple, at least to me, who like billions of other people have seen friends and relatives suffer and die from genetic diseases. Imagine a world where we could eliminate so many childhood cancers, cystic fibrosis, blindness, sickle cell anemia, HIV and God knows how many other diseases with a process that has come to be known as "CRISPR." CRISPR, a revolutionary technology that Dr. Doudna help create, and was awarded the Nobel Peace Prize in chemistry in 2020, that makes heritable changes in one's DNA that would make a genetic disease like sickle cell anemia never infect a person who was destined to suffer from the agonizing disorder.
Well, that technology has arrived and if you don't believe it just look up what the Moderna and Pfizer vaccines, that have proven so effective against the covid-19 virus, are made up of and which has cured cases of HIV and sickle cell anemia. What is so amazing, is how simple it really is according to Dr. Doudna and thousands of other scientists and researches.
But like the vaccines against Covid-19, there are many critics who say we should not mess around with the evolutionary process or that it's against God's will. I don't agree with them and the only real drawback to this amazing technology is the possibility that humans will use it to make 'better' offspring...more intelligent, muscular, and naturally more beautiful children.
Last year, I said the most important book I read was Walter Isaacson's "The Code Breaker," which was mostly about Dr. Doudna, the scientists, and researchers who have help create this technology. Mr. Isaacson's book definitely helped me understand Dr. Doudna and Dr. Sternberg's book, especially the first half that dealt with terms that would have been difficult to understand if I had not read Mr. Isaacson's book.
"A Crack in Creation," and the technology of CRISPR might seem unthinkable to many people, but for me it might very well be the most important scientific and medical discovery in many and many of years...if not the most important medical breakthrough in centuries.
February 23, 2022
Nors ir kaip gerbiu Virginijų Šikšnį, tačiau turiu nusilenkti prieš jį nukonkuravusią gaunant Nobelio premiją šios knygos autorę Jennifer A. Doudna. Taip aiškiai išdėstyti tokią nepaprastą temą kaip genų redagavimas tikrai ne kiekvienam duota.
Beje, siūlau šią knygą pardavinėti ir skaityti kartu su kitos iškilios moters Margaret Atwood parašyta, ir tą pačią temą nagrinėjančia "Oriksė ir Griežlys (Oryx and Crake)".
Beje, siūlau šią knygą pardavinėti ir skaityti kartu su kitos iškilios moters Margaret Atwood parašyta, ir tą pačią temą nagrinėjančia "Oriksė ir Griežlys (Oryx and Crake)".
May 1, 2018
I found this book equally informative and annoying. So much GREAT information. Crispr is nothing short of miraculous. Have you ever studied viruses or plasmids and been amazed at how a virus knows how to cut into a gene sequence and take over a cell and eventually tons of cells inside an entire organisms? This is that on a much more intense scale. Absolutely love this technology!
The writing not was as great as I had hoped. I liked to be wowed without having to sift through bragging or what seem to be very unimpressive philosophical discussions. Even with those limitations, this book is a solid 5 star book.
The writing not was as great as I had hoped. I liked to be wowed without having to sift through bragging or what seem to be very unimpressive philosophical discussions. Even with those limitations, this book is a solid 5 star book.
December 10, 2017
Pretty dry and hyper-technical (or at least poorly explained) re: the details surrounding the CRISPR discovery and how CRISPR works: I learned much, much more from Siddhartha Mukherjee’s “The Gene” re: genetics in general and what all this DNA/RNA stuff does (which then makes understanding CRISPR relatively straightforward). The rest of this book, concerning all the ways CRISPR is (or will be) being used, was much more interesting and worth reading.
If you’re interested in CRISPR but don’t want to get bogged down in the technical details, I would recommend just doing some googling for stories on CRISPR by “The Atlantic” and then skipping to section two of this book after you understand the CRISPR mechanism.
Also, the lawsuit concerning the proper patent holder for CRISPR hangs heavy over Section 1 - it’s painfully obvious the author is using those pages as part of her argument (FWIW - as a lawyer with a strong interest in genetics and a thorough understanding of CRISPR and the patent dispute, I think (and hope!) Jennifer should win).
If you’re interested in CRISPR but don’t want to get bogged down in the technical details, I would recommend just doing some googling for stories on CRISPR by “The Atlantic” and then skipping to section two of this book after you understand the CRISPR mechanism.
Also, the lawsuit concerning the proper patent holder for CRISPR hangs heavy over Section 1 - it’s painfully obvious the author is using those pages as part of her argument (FWIW - as a lawyer with a strong interest in genetics and a thorough understanding of CRISPR and the patent dispute, I think (and hope!) Jennifer should win).
March 26, 2018
I really wanted to love this book... but I didn't. I couldn't help but thinking the whole time I spent reading it that it seemed an awful lot like reading "The Double Helix" by James Watson, who only gave passing mention to the contributions of Rosalind Franklin - whose work without which he and Crick would not have "discovered" that DNA is in a double helix form. Doudna does mention the work of others, but it's clear she considers it her discovery. While I appreciated her attempting to discuss the morality of gene editing in it's various forms (everything from basic discovery life science to somatic cells to germline cells), her "regrets" fell a little flat to me. Working in a lab that uses CRISPR, I was also dismayed by the lack of recognition of the low success rate of doing anything other than disabling genes... it is not as easy and straight forward as she makes it sound. If you're looking for a read about the background and (biased) discovery of CRISPR/Cas9 gene editing, this will do. Anything more and I would look elsewhere.
June 20, 2022
Als Jennifer Doudna 2016 ihre Geschichte der Entdeckung von CRISPR niederschrieb, war ihr bereits klar, dass diese Technologie in ihrer Tragweite mit der Kernenergie vergleichbar ist. Was danach geschah, konnte sie damals noch nicht wissen:
• 2018 kommen Lulu und Nana, die ersten genmanipulierten Zwillinge zur Welt, Amy, ein drittes Baby einige Monate später. Der chinesische Biologe He Jiankui geht dafür drei Jahre ins Gefängnis, denn die Genmanipulation an lebensfähigen Embroys ist in China verboten.
• 2019 kündigt der russische Biologe Denis Rebrikov an, genmanipulierte Babys austragen zu lassen - nähere Informationen sind derzeit nicht zu bekommen.
• 2020 erhält die Autorin gemeinsam mit Emmanuelle Charpentier den Nobelpreis für Chemie.
• Inzwischen kann selbst unsereins für wenig Geld ein DIY-CRISPR-Kit bestellen. Bierhefe mit Quallen-DNA zu manipulieren und damit ein selbstleuchtendes Bier zu brauen, wäre nur eine der lehrreichen Anwendungen.
• Zugleich streiten Bioethiker und andere kluge Köpfe erbittert darüber, ob es nicht unethisch wäre, die Quelle des Lebens selbst und damit die Evolution zu manipulieren, oder ob es nicht unethisch wäre, auf die Ausrottung von Erbkrankheiten oder Überträgern tödlicher Krankheiten wie Mosquitos, also auf die mögliche Beseitigung so vielen Leids zu verzichten.
[Die Nobelpreisträgerinnen Emmanuelle Charpentier und Jennifer A. Doudna]
Jennifer Doudna und ihr Kollege Samuel Sternberg berichten mitreißend und aus sehr persönlicher Perspektive über ihre Arbeit. Im ersten Abschnitt beschreiben sie, wie sich die gegenständliche Forschung in Lauf der Jahre entwickelt hat und parallel dazu, Schritt für Schritt, die Funktionsweise von CRISPR. Das Niveau ist dabei durchaus fordernd, jedenfalls nicht zu oberflächlich. Ich fand diesen Teil schon sehr interessant und konnte eine Menge lernen, unter anderem, dass CRISPR keine neu erfundene Technik ist, sondern ein Mechanismus im Immunsystem von Bakterien, der zu einem Universalwerkzeug adaptiert wurde.
Richtig gut und spannend war dann der zweite Teil. Jennifer Doudna sieht sich plötzlich mit Themen und Fragen konfrontiert, mit denen sie sich nie befasst hat, als sie begann, im Labor harmlose Testreihen durchzuführen. Sie erzählt bemerkenswert offen über ihre Alpträume und inneren Konflikte, zieht durchaus berechtigte Vergleiche mit Oppenheimer. Dabei kommen auch alle medizinischen, sozialen, politischen, ethischen Fragen zur Sprache, die sich jetzt und in Zukunft mit der Anwendung von CRISPR ergeben. Es ist überaus spannend zu lesen, wie sie mit sich selbst ringt, ihre eigene Meinung immer wieder überdenkt und versucht, auch im Austausch mit Kollegen eine tragfähige und verantwortungsvolle Position zu entwickeln. Und sie zeigt, dass es einen gesamtgesellschaftlichen, offenen Prozess der Meinungsbildung zu diesem brisanten Thema braucht.
Nicht alle Anwendungen von CRISPR sind problematisch. Die rote Linie ist der Eingriff in die Keimbahn. Solange 'nur' somatische Zellen manipuliert werden, betrifft das ein Individuum und ist wie so oft eine Frage von Nutzen und Schaden und in der medizinischen Anwendung eine persönliche Entscheidung. Ein Eingriff in die Keimzellen bedeutet jedoch eine vererbbare Veränderung, die an alle folgenden Generationen weitergegeben wird, wenn man so will eine Manipulation der Evolution selbst. Was mich nachdenklich stimmt, ist die Tatsache, dass es der Menschheit in ihrer Geschichte noch immer gelungen ist, eine Technologie zu missbrauchen.
Es ist fast ein Glück, dass die jüngsten Studien an der Genauigkeit der CRISPR-Editierung Zweifel aufkommen lassen, der Schnitt selbst ist zwar punktgenau, die Stränge der DNA müssen aber wieder zusammenwachsen, was die Zelle selbst besorgt, aber offenbar mit erheblichen Unwägbarkeiten. Daraus ergibt sich vielleicht noch eine willkommene Nachdenkpause.
Dieses aufregende und wichtige Sachbuch zu lesen war mir eine Freude. Nicht nur weil ich mein Wissen zur Gentechnologie auf ein neues Level bringen und meine Meinung dazu differenzieren konnte, es war auch ein besonderes Erlebnis, so hautnah am Denken und Fühlen dieser klugen, weitsichtigen und bewundernswerten Frau teilhaben zu dürfen.
• 2018 kommen Lulu und Nana, die ersten genmanipulierten Zwillinge zur Welt, Amy, ein drittes Baby einige Monate später. Der chinesische Biologe He Jiankui geht dafür drei Jahre ins Gefängnis, denn die Genmanipulation an lebensfähigen Embroys ist in China verboten.
• 2019 kündigt der russische Biologe Denis Rebrikov an, genmanipulierte Babys austragen zu lassen - nähere Informationen sind derzeit nicht zu bekommen.
• 2020 erhält die Autorin gemeinsam mit Emmanuelle Charpentier den Nobelpreis für Chemie.
• Inzwischen kann selbst unsereins für wenig Geld ein DIY-CRISPR-Kit bestellen. Bierhefe mit Quallen-DNA zu manipulieren und damit ein selbstleuchtendes Bier zu brauen, wäre nur eine der lehrreichen Anwendungen.
• Zugleich streiten Bioethiker und andere kluge Köpfe erbittert darüber, ob es nicht unethisch wäre, die Quelle des Lebens selbst und damit die Evolution zu manipulieren, oder ob es nicht unethisch wäre, auf die Ausrottung von Erbkrankheiten oder Überträgern tödlicher Krankheiten wie Mosquitos, also auf die mögliche Beseitigung so vielen Leids zu verzichten.
[Die Nobelpreisträgerinnen Emmanuelle Charpentier und Jennifer A. Doudna]
Jennifer Doudna und ihr Kollege Samuel Sternberg berichten mitreißend und aus sehr persönlicher Perspektive über ihre Arbeit. Im ersten Abschnitt beschreiben sie, wie sich die gegenständliche Forschung in Lauf der Jahre entwickelt hat und parallel dazu, Schritt für Schritt, die Funktionsweise von CRISPR. Das Niveau ist dabei durchaus fordernd, jedenfalls nicht zu oberflächlich. Ich fand diesen Teil schon sehr interessant und konnte eine Menge lernen, unter anderem, dass CRISPR keine neu erfundene Technik ist, sondern ein Mechanismus im Immunsystem von Bakterien, der zu einem Universalwerkzeug adaptiert wurde.
Richtig gut und spannend war dann der zweite Teil. Jennifer Doudna sieht sich plötzlich mit Themen und Fragen konfrontiert, mit denen sie sich nie befasst hat, als sie begann, im Labor harmlose Testreihen durchzuführen. Sie erzählt bemerkenswert offen über ihre Alpträume und inneren Konflikte, zieht durchaus berechtigte Vergleiche mit Oppenheimer. Dabei kommen auch alle medizinischen, sozialen, politischen, ethischen Fragen zur Sprache, die sich jetzt und in Zukunft mit der Anwendung von CRISPR ergeben. Es ist überaus spannend zu lesen, wie sie mit sich selbst ringt, ihre eigene Meinung immer wieder überdenkt und versucht, auch im Austausch mit Kollegen eine tragfähige und verantwortungsvolle Position zu entwickeln. Und sie zeigt, dass es einen gesamtgesellschaftlichen, offenen Prozess der Meinungsbildung zu diesem brisanten Thema braucht.
Nicht alle Anwendungen von CRISPR sind problematisch. Die rote Linie ist der Eingriff in die Keimbahn. Solange 'nur' somatische Zellen manipuliert werden, betrifft das ein Individuum und ist wie so oft eine Frage von Nutzen und Schaden und in der medizinischen Anwendung eine persönliche Entscheidung. Ein Eingriff in die Keimzellen bedeutet jedoch eine vererbbare Veränderung, die an alle folgenden Generationen weitergegeben wird, wenn man so will eine Manipulation der Evolution selbst. Was mich nachdenklich stimmt, ist die Tatsache, dass es der Menschheit in ihrer Geschichte noch immer gelungen ist, eine Technologie zu missbrauchen.
Es ist fast ein Glück, dass die jüngsten Studien an der Genauigkeit der CRISPR-Editierung Zweifel aufkommen lassen, der Schnitt selbst ist zwar punktgenau, die Stränge der DNA müssen aber wieder zusammenwachsen, was die Zelle selbst besorgt, aber offenbar mit erheblichen Unwägbarkeiten. Daraus ergibt sich vielleicht noch eine willkommene Nachdenkpause.
Dieses aufregende und wichtige Sachbuch zu lesen war mir eine Freude. Nicht nur weil ich mein Wissen zur Gentechnologie auf ein neues Level bringen und meine Meinung dazu differenzieren konnte, es war auch ein besonderes Erlebnis, so hautnah am Denken und Fühlen dieser klugen, weitsichtigen und bewundernswerten Frau teilhaben zu dürfen.
November 24, 2018
"CRISPR Cas 9. This book is its story and mine. It is also yours. Because it won’t be long before the repercussions from this technology reach your doorstep too.”
Die Genschere CIRSPR CAS9 ist wohl die größte und wichtigste wissenschaftliche Entdeckung unseres Jahrhunderts, vergleichbar mit der Entdeckung der DNA durch Watson und Crick (naja eigentlich durch Rosalind Franklin, aber dieses Fass will ich jetzt nicht aufmachen) oder der Entwicklung rekombinanter DNA.
Als Jennifer Doudna, Leiterin eines Forschungslabors an der University of Berkely, 2006 das erste mal von Bakterien erfährt die ein scheinbar sehr spezielles Abwehrsystem gegen Viren entwickelt haben, das sich irgendwie nach "crisper" anhört, ist dieser Gegenstand noch so exotisch, das weltweit noch nicht einmal hundert Teams daran forschen.
Nach jahrelanger Forschung mit herben Rückschlägen gelingt ihr 2012 zusammen mit Emmannuelle Charpentier der Durchbruch. Sie veröffentlichen ein Paper zur Entdeckung der Genschere CRISPR CAS9 in der Zeitschrift Science, welches, um es mal pathetisch auszudrücken, die Welt verändern wird.
Mittlerweile, fünf Jahre später, ist die Forschung mit CRISPR Nr.1 im biotechnologischen Bereich.
Vielleicht brauchen wir bald keine Spenderorgane von Menschen mehr, Schweineorgane wurden schon erfolgreich "humanisiert" um in Zukunft für Transplantationen verwendet zu werden. Die Fortschritte reichen bereits soweit, dass erste klinische Studien mit Menschen, zur Heilung genetischer Krankheiten, geplant sind. Versuchen mit menschlichen Embryonen wurden bereits zu Beta-Thalassämie durchgeführt, allerdings mit mäßigem Ergebnis. Es wird noch eine ganze Weile dauern bis wir genetische Erbkrankheiten vollständig heilen können, den Schlüssel halten wir in der Hand und wenn man selbst Betroffener ist, kann dieser Fortschritt gar nicht schnell genug kommen.
Einige Dinge hören sich nach Science-Fiction an, wie bpsw. die De-extinction, wo es darum geht ausgestorbene Tiere wie den Dodo oder sogar das Mammut zurückzubringen. CRISPR birgt aber auch das Risiko Spezies auszulöschen. Bei Moskitos die Malaria übertragen, wird tatsächlich daran geforscht und überlegt, diese auszurotten. Man muss lediglich einer kritische Anzahl an Individuen im Labor ein letales Gen einfügen, die Tiere freilassen und die Selektion den Rest erledigen lassen. Und wenn man dann irgendwann doch wieder Bock auf Moskitos hat, bringt man sie halt wieder zurück.
Das klingt alles ziemlich krass, was es auch ist. Genau deshalb hat es sich Jennifer Doudna zur Aufgabe gemacht über diese Technologie aufzuklären und dieses Buch zu schreiben.
Ist CRISPR nun der heilige Gral oder die Büchse der Pandora? Diese Frage beantwortet Jennifer Doudna nicht, sie möchte vielmehr jedem die Informationen über mögliche Auswirkungen (positiv wie negativ) an die Hand geben, die einen befähigen sich selbst eine Meinung bilden zu können. Denn diese Technologie betrifft nicht allein die Wissenschaft und Wissenschaftler, sie wird eine Auswirkung auf jeden einzelnen in unserer Gesellschaft haben, ob derjenige dies nun mitbekommt oder nicht. Doudna betont mehrmals dass es ihr wichtig ist, die Diskussion über Chancen und Risiken, über soziale Auswirkungen, über notwendige gesetzliche Regelungen lieber früher als später anzufangen. Ihrer Meinung nach (und auch meiner) sollte täglich im Fernsehen, in Zeitungen in allen verfügbaren Medien über Forschung berichtet werden. Sodass diese Information wirklich an niemandem mehr vorbei gehen kann und jeder das Recht und die Möglichkeit hat, sich eine fundierte Meinung zu bilden, oder zumindest über diese Technologie Bescheid wissen.
Ich finde es wirklich bedenklich dass dieses Buch bisher nicht auf deutsch erschienen ist, das zeigt nur die fehlende Relevanz dieses Themas außerhalb des Wissenschaftsbetriebs.
Um diese Rezension mit Jennifer Doudnas Worten abzuschließen:
“The power to control our species’ genetic future is awesome and terrifying. Deciding how to handle it may be the biggest challenge we have ever faced.”
Die Genschere CIRSPR CAS9 ist wohl die größte und wichtigste wissenschaftliche Entdeckung unseres Jahrhunderts, vergleichbar mit der Entdeckung der DNA durch Watson und Crick (naja eigentlich durch Rosalind Franklin, aber dieses Fass will ich jetzt nicht aufmachen) oder der Entwicklung rekombinanter DNA.
Als Jennifer Doudna, Leiterin eines Forschungslabors an der University of Berkely, 2006 das erste mal von Bakterien erfährt die ein scheinbar sehr spezielles Abwehrsystem gegen Viren entwickelt haben, das sich irgendwie nach "crisper" anhört, ist dieser Gegenstand noch so exotisch, das weltweit noch nicht einmal hundert Teams daran forschen.
Nach jahrelanger Forschung mit herben Rückschlägen gelingt ihr 2012 zusammen mit Emmannuelle Charpentier der Durchbruch. Sie veröffentlichen ein Paper zur Entdeckung der Genschere CRISPR CAS9 in der Zeitschrift Science, welches, um es mal pathetisch auszudrücken, die Welt verändern wird.
Mittlerweile, fünf Jahre später, ist die Forschung mit CRISPR Nr.1 im biotechnologischen Bereich.
Vielleicht brauchen wir bald keine Spenderorgane von Menschen mehr, Schweineorgane wurden schon erfolgreich "humanisiert" um in Zukunft für Transplantationen verwendet zu werden. Die Fortschritte reichen bereits soweit, dass erste klinische Studien mit Menschen, zur Heilung genetischer Krankheiten, geplant sind. Versuchen mit menschlichen Embryonen wurden bereits zu Beta-Thalassämie durchgeführt, allerdings mit mäßigem Ergebnis. Es wird noch eine ganze Weile dauern bis wir genetische Erbkrankheiten vollständig heilen können, den Schlüssel halten wir in der Hand und wenn man selbst Betroffener ist, kann dieser Fortschritt gar nicht schnell genug kommen.
Einige Dinge hören sich nach Science-Fiction an, wie bpsw. die De-extinction, wo es darum geht ausgestorbene Tiere wie den Dodo oder sogar das Mammut zurückzubringen. CRISPR birgt aber auch das Risiko Spezies auszulöschen. Bei Moskitos die Malaria übertragen, wird tatsächlich daran geforscht und überlegt, diese auszurotten. Man muss lediglich einer kritische Anzahl an Individuen im Labor ein letales Gen einfügen, die Tiere freilassen und die Selektion den Rest erledigen lassen. Und wenn man dann irgendwann doch wieder Bock auf Moskitos hat, bringt man sie halt wieder zurück.
Das klingt alles ziemlich krass, was es auch ist. Genau deshalb hat es sich Jennifer Doudna zur Aufgabe gemacht über diese Technologie aufzuklären und dieses Buch zu schreiben.
Ist CRISPR nun der heilige Gral oder die Büchse der Pandora? Diese Frage beantwortet Jennifer Doudna nicht, sie möchte vielmehr jedem die Informationen über mögliche Auswirkungen (positiv wie negativ) an die Hand geben, die einen befähigen sich selbst eine Meinung bilden zu können. Denn diese Technologie betrifft nicht allein die Wissenschaft und Wissenschaftler, sie wird eine Auswirkung auf jeden einzelnen in unserer Gesellschaft haben, ob derjenige dies nun mitbekommt oder nicht. Doudna betont mehrmals dass es ihr wichtig ist, die Diskussion über Chancen und Risiken, über soziale Auswirkungen, über notwendige gesetzliche Regelungen lieber früher als später anzufangen. Ihrer Meinung nach (und auch meiner) sollte täglich im Fernsehen, in Zeitungen in allen verfügbaren Medien über Forschung berichtet werden. Sodass diese Information wirklich an niemandem mehr vorbei gehen kann und jeder das Recht und die Möglichkeit hat, sich eine fundierte Meinung zu bilden, oder zumindest über diese Technologie Bescheid wissen.
Ich finde es wirklich bedenklich dass dieses Buch bisher nicht auf deutsch erschienen ist, das zeigt nur die fehlende Relevanz dieses Themas außerhalb des Wissenschaftsbetriebs.
Um diese Rezension mit Jennifer Doudnas Worten abzuschließen:
“The power to control our species’ genetic future is awesome and terrifying. Deciding how to handle it may be the biggest challenge we have ever faced.”
December 13, 2018
Jennifer Doudna didnt set out with the intent to create something so world changing when she became a biochemist. In fact, genetics wasnt even on her radar. Instead she was interested in bacteria and viruses. It was through her research on viruses that she accidentally found herself in this entirely different scientific arena. From there CRISPR was born, and the revolution of gene editing has been spreading its veins into just about every field of research and medicine.
I loved this book because it gives a pretty comprehensive background on cell biology and biochemistry without feeling like a university lecture. Interspersed between the scientific rundowns are bits of commentary and history from doudna. The entire first part of the book talks about the different mechanisms that were studied for gene editing before CRISPR reigned king.
The middle focuses on CRISPR itself and the multitude of variois applications in which it can be applied. Along with more play by play of how Doudna navigated the new excitement and notoriety her discovery is getting, she also comments about her concerns over policy and regulation.
The last part of the book jumps into the policy and regulation with more force and consternation. Finally getting into the ethics surrounding the use of gene editing technology and the dystopian future it might bring. How do you control such powerful technology? How do you make sure it isn't being taken advantage of for personal gain and fame? Just a week after i finished reading this, a Chinese man reported having produced the first ever CRISPR gene-edited babies (link below to article) This is a far different scenario than the "designer babies" talked of with normal IVF (where an embryos DNA is analyzed pre-implantation and the embryos that fit the genetic markers selected for most closely are chose to be inserted during the procedure - i.e. no actual genetic changes are physically made)
Obviously, getting to the point where gene editing on embryos can happen has always been considered the end game of this research. Reading Doudna's book will put into perspective how far off we really are to being able to do this without massive consequences. In the later chapters she talks about the "gene gap" where we may essentially create a whole new marginalized group of people. The one who can afford to do gene editing are the "haves" and everyone else are the "have nots". This poses as a dangerously high possibility in our society with an ever widing income disparity.
The rogue scientist (who didn't even publish his work, rather presented his findings on slides via youtube...smh) timed his big reveal to happem just before the Second International Summit on Human Genome Editing. I was invited to watch remotely since it was happening across the world in Hong Kong, and from what I gathered of the people there was an overall sense of anger, distress, and bewilderment.
It's because of this recent mishap that this book should be more widely acknowledged and understood. Outside the scientific community, i can bet many people are still confused about what the crispr-cas9 system does. However, at some point in our near future this system is going to become one of the most influential technologies of our time, whether or not we are ready for it.
I loved this book because it gives a pretty comprehensive background on cell biology and biochemistry without feeling like a university lecture. Interspersed between the scientific rundowns are bits of commentary and history from doudna. The entire first part of the book talks about the different mechanisms that were studied for gene editing before CRISPR reigned king.
The middle focuses on CRISPR itself and the multitude of variois applications in which it can be applied. Along with more play by play of how Doudna navigated the new excitement and notoriety her discovery is getting, she also comments about her concerns over policy and regulation.
The last part of the book jumps into the policy and regulation with more force and consternation. Finally getting into the ethics surrounding the use of gene editing technology and the dystopian future it might bring. How do you control such powerful technology? How do you make sure it isn't being taken advantage of for personal gain and fame? Just a week after i finished reading this, a Chinese man reported having produced the first ever CRISPR gene-edited babies (link below to article) This is a far different scenario than the "designer babies" talked of with normal IVF (where an embryos DNA is analyzed pre-implantation and the embryos that fit the genetic markers selected for most closely are chose to be inserted during the procedure - i.e. no actual genetic changes are physically made)
Obviously, getting to the point where gene editing on embryos can happen has always been considered the end game of this research. Reading Doudna's book will put into perspective how far off we really are to being able to do this without massive consequences. In the later chapters she talks about the "gene gap" where we may essentially create a whole new marginalized group of people. The one who can afford to do gene editing are the "haves" and everyone else are the "have nots". This poses as a dangerously high possibility in our society with an ever widing income disparity.
The rogue scientist (who didn't even publish his work, rather presented his findings on slides via youtube...smh) timed his big reveal to happem just before the Second International Summit on Human Genome Editing. I was invited to watch remotely since it was happening across the world in Hong Kong, and from what I gathered of the people there was an overall sense of anger, distress, and bewilderment.
It's because of this recent mishap that this book should be more widely acknowledged and understood. Outside the scientific community, i can bet many people are still confused about what the crispr-cas9 system does. However, at some point in our near future this system is going to become one of the most influential technologies of our time, whether or not we are ready for it.
August 16, 2020
A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution, Jennifer A. Doudna, Samuel H. Sternberg, 2017, 281pp. (246pp. text + endmatter), ISBN 9780544716940, Dewey 576.5072, Library-of-Congress QH440
The authors are biochemists.
Viruses can splice new genetic information into the DNA of host cells. p. 16. Eight percent of the human genome is viral. p. 19.
Streptococcus thermophilus makes milk into yogurt or cheese. Streptococcus pyogenes causes .5 million human deaths annually. It causes strep throat, scarlet fever, toxic shock syndrome, and necrotizing fasciitis (flesh-eating bacteria). The two species of bacteria contain "all the same genes." pp. 72-73.
Bacteriophages--bacteria-destroying viruses--are the most prevalent life forms on Earth. They outnumber bacteria 10-to-1. Every day, 40% of all ocean bacteria are destroyed by phages. p. 48.
Bacterial DNA contains "Clustered Regularly Interspaced Short Palindromic Repeats" (CRISPR): between the repeated palindromes are snippets of DNA the bacteria have absorbed from viruses. The bacteria use these to match with and recognize attacking viral DNA; then to cut and destroy the attacking viral DNA. CRISPR is part of the bacterium's immune system. pp. 43-59. The bacteria's DNA is a template to make 2 kinds of RNA, and to make various enzymes. The RNA identifies and cuts the attacking viral DNA; the enzymes complete the destruction. pp. 62-81.
By modifying the swatch of DNA it matches, the CRISPR RNA, with its "tracrRNA," can be used to snip out /any/ bit of DNA. Not just viral DNA. The technique can work for human DNA too. pp. 81ff.
The author and her colleagues submitted their paper suggesting this to /Science/, June 8, 2012. It was published 20 days later and changed the field. p. 85.
"But should we?" pp. 113-246.
The author is oddly worrisome about the prospect that parents may interfere with nature to the extent of preventing their unborn child from being born with a congenital defect. Yet she's oddly OK with the idea of using the techniques to edit genes to cause the extinction of mosquitoes (and all the life forms that depend on them). She feels that /she/ should have a say in how people are permitted to use these techniques.
In any case, Pandora's box is open. Crops, domestic animals, wild animals, and humans are being modified using the techniques.
The author's description of the pace of advance makes this, her 2017 book, seem already dated in 2019.
The authors are biochemists.
Viruses can splice new genetic information into the DNA of host cells. p. 16. Eight percent of the human genome is viral. p. 19.
Streptococcus thermophilus makes milk into yogurt or cheese. Streptococcus pyogenes causes .5 million human deaths annually. It causes strep throat, scarlet fever, toxic shock syndrome, and necrotizing fasciitis (flesh-eating bacteria). The two species of bacteria contain "all the same genes." pp. 72-73.
Bacteriophages--bacteria-destroying viruses--are the most prevalent life forms on Earth. They outnumber bacteria 10-to-1. Every day, 40% of all ocean bacteria are destroyed by phages. p. 48.
Bacterial DNA contains "Clustered Regularly Interspaced Short Palindromic Repeats" (CRISPR): between the repeated palindromes are snippets of DNA the bacteria have absorbed from viruses. The bacteria use these to match with and recognize attacking viral DNA; then to cut and destroy the attacking viral DNA. CRISPR is part of the bacterium's immune system. pp. 43-59. The bacteria's DNA is a template to make 2 kinds of RNA, and to make various enzymes. The RNA identifies and cuts the attacking viral DNA; the enzymes complete the destruction. pp. 62-81.
By modifying the swatch of DNA it matches, the CRISPR RNA, with its "tracrRNA," can be used to snip out /any/ bit of DNA. Not just viral DNA. The technique can work for human DNA too. pp. 81ff.
The author and her colleagues submitted their paper suggesting this to /Science/, June 8, 2012. It was published 20 days later and changed the field. p. 85.
"But should we?" pp. 113-246.
The author is oddly worrisome about the prospect that parents may interfere with nature to the extent of preventing their unborn child from being born with a congenital defect. Yet she's oddly OK with the idea of using the techniques to edit genes to cause the extinction of mosquitoes (and all the life forms that depend on them). She feels that /she/ should have a say in how people are permitted to use these techniques.
In any case, Pandora's box is open. Crops, domestic animals, wild animals, and humans are being modified using the techniques.
The author's description of the pace of advance makes this, her 2017 book, seem already dated in 2019.
January 9, 2018
This is simply amazing research and I am in awe of Doudna. The book is really sciency, which is good, but I was less interested in the play by play than in the possibilities (no, I am not a scientist). Nevertheless, a great read.
May 15, 2018
If I have one big takeaway from this book, it's this: there needs to be a LOT more interaction between scientists and sociologists. While I appreciated and was fascinated by the science detailed in this book, I was frankly incredulous about Doudna's reaction to the effects CRISPR have wrought in the world because I do not see how anyone could have failed to see them coming. Her obliviousness (honestly, I don't know what else to call it) lends credence to the idea that scientists are disconnected from the world because they spend all their time holed up in their labs conducting experiments.
Now, I want to say a couple of things before I get deeper into what I found so disturbing about this book. I tend to be something of an idealist myself, so my cynical view of Doudna's idealism took me aback. I'm also a huge advocate for science and am dismayed by the growing ignorance of science I see manifesting in the U.S. My argument is not that people shouldn't try to make the world a better place, or they shouldn't be focused on finding ways of improving the human condition, or that science is evil. I do not think the importance of science can be overstated. However, I have serious concerns about unfettered science. Didn't humans' experiences with the nuclear arms race and the fundamental ways in which that has changed our world teach us a lesson we should not have forgotten? When science is divorced from sociology and politics, chaos ensues.
The idea of editing the human germline in order to prevent future suffering is laudable. I truly believe that. There are a lot of horrifying diseases that affect humans in unthinkable ways, and I am all for finding better treatments if not cures for these diseases. However, humans never seem to learn that when they mess with nature, the results are not usually favorable to us. You need look only at climate change, invasive species, and the rise of antibiotic-resistant bacteria to see abundant evidence of this. Editing the germline might sound like a great idea, but the problem is we have no way of knowing what effects that editing might have a few generations down the line. What if in trying to eradicate known diseases, we create a whole new raft of even more powerful, even more horrifying, diseases? I'm not saying scientists shouldn't work to find solutions to these problems. What I am saying is that there needs to be a lot of thought given to these things. Doudna points out throughout the book that scientists need to think about not whether they can do something, but whether they should, yet she seems to reach the same conclusion every time: well, there could be bad consequences, but we should. I'm not comfortable with that mindset.
I also think Doudna fails to look at the larger picture in many cases. She touts GMOs, but using the argument that they're safe for human consumption. Okay, but what about the problem of mega corporations patenting the genes for these GMO plants? What about the plight of farmers who are sued by these corporations when seeds from said plants drift into their fields? What about the rise of super weeds, which have developed resistance to the pesticides GMO seeds were engineered to resist? What about how these genetically engineered plants affect the larger ecosystem? Doudna talks about unintended consequences, but in a very shallow way. When humans play around with genes, we're fundamentally changing nature in ways nature might not be prepared for, and it only stands to reason that we're going to interfere with evolution in other unforeseen ways, as we did by bringing non-native plants to many areas only to find those plants choking out native vegetation. Human don't tend to tread lightly on our delicate planet; instead, we have a habit of trouncing all over it. I was very put off by her lack of respect for the sanctity of any form of life other than human life.
I think what bothered me most of all, though, was that Doudna fails to think about the social implications of gene editing in a deep way. Yes, she does address concerns about inequality, but to me it sounded like her ultimate conclusion was, "Well, but humans are good, so we won't do that." Humans may be good for the most part, but there are plenty of bad humans, and those humans are going to have no compunction about exploiting technological advances to their own favor. The fact that she didn't even stop to think that terrorists might look to exploit gene editing left me floored. How could she not have foreseen that? Those who seeks to destroy will always look for ways to weaponize new technological advances, and I was kind of appalled that Doudna didn't anticipate that.
I'm also skeptical of her views about how gene editing may further the field of medicine. There's no doubt a good number of people would benefit from these technologies, but she glosses over who stands to benefit from them. She does point out the possibility of further societal stratification based on genes, but I don't think she gives that point enough weight. One look at the current state of health care in America will tell you everything you need to know about who will ultimately benefit from gene editing, and it's not going to be the poorest of the poor. We live in a society where many of our fellow citizens can't access even the most basic health care services, and I frankly think she's willfully ignoring this when she touts the marvels of gene editing. If some members of society can't even afford to seek medical care when they have the flu, in what world does she think they're going to benefit from gene editing?
Lastly, I also think she glides right over questions of "designer" babies. Of course this technology will be developed. We already live in a world where people abandon or kill babies who don't have "desirable" traits, so how would she think gene editing would change this? As with health care, once this technology becomes a reality, the rich will benefit the most. The thought of a world where the richest have many genetic benefits, both from a health perspective and from the perspective of their possessing extraordinary intelligence or strength or whatever ought to keep Doudna up at night. There's a reason why science fiction writers tend to sound the alarm when it comes to technological developments, and it isn't because ours is a world where everyone benefits equally from technological advances.
Honestly, the book kind of left me with a bad taste in my mouth. I can see how when scientists are caught up in their research, they don't see the larger picture of how their actions will affect others. After all, scientists are human, and humans in general are bad at that. I will give credit where it's due and say I think it's laudable that Doudna wants the public to have better access to information, that she thinks scientists need to engage with the public more, and that she thinks everyone should have a stake in deciding how technology should be applied, not just those who develop it, but the cynical side of me says it's too little too late. Pandora's box has been opened. Now more than ever, science needs more oversight, and scientific ethics need to be given far more weight than they have been. I'm not advocating for holding back progress, but I firmly believe that we need loud, informed voices helping to guide that progress, for the good of all.
Now, I want to say a couple of things before I get deeper into what I found so disturbing about this book. I tend to be something of an idealist myself, so my cynical view of Doudna's idealism took me aback. I'm also a huge advocate for science and am dismayed by the growing ignorance of science I see manifesting in the U.S. My argument is not that people shouldn't try to make the world a better place, or they shouldn't be focused on finding ways of improving the human condition, or that science is evil. I do not think the importance of science can be overstated. However, I have serious concerns about unfettered science. Didn't humans' experiences with the nuclear arms race and the fundamental ways in which that has changed our world teach us a lesson we should not have forgotten? When science is divorced from sociology and politics, chaos ensues.
The idea of editing the human germline in order to prevent future suffering is laudable. I truly believe that. There are a lot of horrifying diseases that affect humans in unthinkable ways, and I am all for finding better treatments if not cures for these diseases. However, humans never seem to learn that when they mess with nature, the results are not usually favorable to us. You need look only at climate change, invasive species, and the rise of antibiotic-resistant bacteria to see abundant evidence of this. Editing the germline might sound like a great idea, but the problem is we have no way of knowing what effects that editing might have a few generations down the line. What if in trying to eradicate known diseases, we create a whole new raft of even more powerful, even more horrifying, diseases? I'm not saying scientists shouldn't work to find solutions to these problems. What I am saying is that there needs to be a lot of thought given to these things. Doudna points out throughout the book that scientists need to think about not whether they can do something, but whether they should, yet she seems to reach the same conclusion every time: well, there could be bad consequences, but we should. I'm not comfortable with that mindset.
I also think Doudna fails to look at the larger picture in many cases. She touts GMOs, but using the argument that they're safe for human consumption. Okay, but what about the problem of mega corporations patenting the genes for these GMO plants? What about the plight of farmers who are sued by these corporations when seeds from said plants drift into their fields? What about the rise of super weeds, which have developed resistance to the pesticides GMO seeds were engineered to resist? What about how these genetically engineered plants affect the larger ecosystem? Doudna talks about unintended consequences, but in a very shallow way. When humans play around with genes, we're fundamentally changing nature in ways nature might not be prepared for, and it only stands to reason that we're going to interfere with evolution in other unforeseen ways, as we did by bringing non-native plants to many areas only to find those plants choking out native vegetation. Human don't tend to tread lightly on our delicate planet; instead, we have a habit of trouncing all over it. I was very put off by her lack of respect for the sanctity of any form of life other than human life.
I think what bothered me most of all, though, was that Doudna fails to think about the social implications of gene editing in a deep way. Yes, she does address concerns about inequality, but to me it sounded like her ultimate conclusion was, "Well, but humans are good, so we won't do that." Humans may be good for the most part, but there are plenty of bad humans, and those humans are going to have no compunction about exploiting technological advances to their own favor. The fact that she didn't even stop to think that terrorists might look to exploit gene editing left me floored. How could she not have foreseen that? Those who seeks to destroy will always look for ways to weaponize new technological advances, and I was kind of appalled that Doudna didn't anticipate that.
I'm also skeptical of her views about how gene editing may further the field of medicine. There's no doubt a good number of people would benefit from these technologies, but she glosses over who stands to benefit from them. She does point out the possibility of further societal stratification based on genes, but I don't think she gives that point enough weight. One look at the current state of health care in America will tell you everything you need to know about who will ultimately benefit from gene editing, and it's not going to be the poorest of the poor. We live in a society where many of our fellow citizens can't access even the most basic health care services, and I frankly think she's willfully ignoring this when she touts the marvels of gene editing. If some members of society can't even afford to seek medical care when they have the flu, in what world does she think they're going to benefit from gene editing?
Lastly, I also think she glides right over questions of "designer" babies. Of course this technology will be developed. We already live in a world where people abandon or kill babies who don't have "desirable" traits, so how would she think gene editing would change this? As with health care, once this technology becomes a reality, the rich will benefit the most. The thought of a world where the richest have many genetic benefits, both from a health perspective and from the perspective of their possessing extraordinary intelligence or strength or whatever ought to keep Doudna up at night. There's a reason why science fiction writers tend to sound the alarm when it comes to technological developments, and it isn't because ours is a world where everyone benefits equally from technological advances.
Honestly, the book kind of left me with a bad taste in my mouth. I can see how when scientists are caught up in their research, they don't see the larger picture of how their actions will affect others. After all, scientists are human, and humans in general are bad at that. I will give credit where it's due and say I think it's laudable that Doudna wants the public to have better access to information, that she thinks scientists need to engage with the public more, and that she thinks everyone should have a stake in deciding how technology should be applied, not just those who develop it, but the cynical side of me says it's too little too late. Pandora's box has been opened. Now more than ever, science needs more oversight, and scientific ethics need to be given far more weight than they have been. I'm not advocating for holding back progress, but I firmly believe that we need loud, informed voices helping to guide that progress, for the good of all.
December 4, 2019
I am very picky with what I bring on airplanes.
As precious overhead storage space is never guaranteed, I whittle down my carryon to the barest of underseat essentials. Space gets tight, quarters get cramped, tempers get short, and so my reading material must pack a mega payload of enjoyment to qualify as flightworthy.
Nonfiction is my go-to, especially readable contemporary nonfiction in which the narrator takes an active role in the story. It needs to be dense enough that I feel I'm learning something new, and also informal enough to set down and pick up in a moment, should my two-year-old need his nose blown or his younger sister need a diaper change mid-flight.
One side effect of this compulsion is the permanent association between place and trivia that is burned into my mind. So, for example, whenever I land in Denver I am flooded with factoids about battle-ready fabric courtesy of Mary Roach's Grunt . Chicago's Midway brings back Dr. Mutter's Marvels . Thanks to this delightful book, O'hare will be "the DNA airport."
(My favorite thing to read on my rare childless flights is "The Classics" because I know I am going to be stuck in one place and one position for several hours at a time, so it's a good opportunity to chip away at those quote-unquote important works.)
A Crack in Creation's content is exciting and its tone is energetic. The science of genetic research has grown by leaps and bounds in recent decades, and this book helps covey the dizzying speed of progress. In short, the authors make learning fun! It's also a great peek into the subject of Bioethics and begins to raise questions about the philosophical implications of unchecked technology use, even if intended for improvements.
As precious overhead storage space is never guaranteed, I whittle down my carryon to the barest of underseat essentials. Space gets tight, quarters get cramped, tempers get short, and so my reading material must pack a mega payload of enjoyment to qualify as flightworthy.
Nonfiction is my go-to, especially readable contemporary nonfiction in which the narrator takes an active role in the story. It needs to be dense enough that I feel I'm learning something new, and also informal enough to set down and pick up in a moment, should my two-year-old need his nose blown or his younger sister need a diaper change mid-flight.
One side effect of this compulsion is the permanent association between place and trivia that is burned into my mind. So, for example, whenever I land in Denver I am flooded with factoids about battle-ready fabric courtesy of Mary Roach's Grunt . Chicago's Midway brings back Dr. Mutter's Marvels . Thanks to this delightful book, O'hare will be "the DNA airport."
(My favorite thing to read on my rare childless flights is "The Classics" because I know I am going to be stuck in one place and one position for several hours at a time, so it's a good opportunity to chip away at those quote-unquote important works.)
A Crack in Creation's content is exciting and its tone is energetic. The science of genetic research has grown by leaps and bounds in recent decades, and this book helps covey the dizzying speed of progress. In short, the authors make learning fun! It's also a great peek into the subject of Bioethics and begins to raise questions about the philosophical implications of unchecked technology use, even if intended for improvements.
October 14, 2017
If you haven’t heard of CRISPR before, chances are you’ll be hearing of it again pretty soon. It’s starting to be used in clinical trials to edit the genes of human embryos, and it’s already being used in countless research projects. It’s an amazing tool which could completely revolutionise gene editing, allowing very precise changes to be made with very little unintended impact. Doudna is one of the people who has been involved in developing CRISPR and recognising its potential, and her book covers exactly how it works and the potential it has — and some of the philosophical questions around how we’re going to use it.
The explanations of how CRISPR works are perfect: clear and precise, along with diagrams which help elucidate the processes described. Even if you already know a little about CRISPR, this account will probably help you understand just how it works and why it’s so revolutionary.
As far as the ethics/philosophy goes, Doudna says nothing particularly revolutionary. (It’s very much framed as her book, despite Sternberg’s involvement.) What struck me especially was her conviction that this is a decision that has to be made by people in general, not just scientists — it’s something I agree with very much, and why I have a science blog of my own.
An important read, I think — even if you’re not hugely into science/gene editing.
Reviewed for The Bibliophibian.
The explanations of how CRISPR works are perfect: clear and precise, along with diagrams which help elucidate the processes described. Even if you already know a little about CRISPR, this account will probably help you understand just how it works and why it’s so revolutionary.
As far as the ethics/philosophy goes, Doudna says nothing particularly revolutionary. (It’s very much framed as her book, despite Sternberg’s involvement.) What struck me especially was her conviction that this is a decision that has to be made by people in general, not just scientists — it’s something I agree with very much, and why I have a science blog of my own.
An important read, I think — even if you’re not hugely into science/gene editing.
Reviewed for The Bibliophibian.
July 11, 2017
The biology of CRISPR/CAS in book are well done, but the ethics of its use less so -both in terms of clarity and thoughtfulness (not surprising given authors' background), but also some very wishful thinking (including little consideration of the inevitability of the race to the bottom (due market forces and large differences in regulation among countries). nonetheless, cat is out of bag, so the limits of the technology will ultimately decide where this goes.
April 16, 2020
This book will tell you everything you will ever need to know about CRISPR, the revolutionary new, and controversial, gene-editing tool. Doudna give a good history and background of the science leading up to her team's discoveries...BUT I must warn you that you need to know something about microbiology to understand this process. Without it, you're pretty much lost.
The other issue I have with this book is that Doudna does not delve very deeply into the ethical implications of editing our DNA...much less the moral challenges. As a matter of fact, she pretty much says almost nothing any religious objections to this process, except to say that many in the Judeo-Christian tradition might have a problem with the entire issue-duh!!
So as a clear history (esp. in Part I) the book is great and will teach you a lot if you give it a close reading. But regarding the future, we need much more ethical and moral investigation of this process which could eventually change the very makeup of all human life.
The other issue I have with this book is that Doudna does not delve very deeply into the ethical implications of editing our DNA...much less the moral challenges. As a matter of fact, she pretty much says almost nothing any religious objections to this process, except to say that many in the Judeo-Christian tradition might have a problem with the entire issue-duh!!
So as a clear history (esp. in Part I) the book is great and will teach you a lot if you give it a close reading. But regarding the future, we need much more ethical and moral investigation of this process which could eventually change the very makeup of all human life.
August 21, 2017
I want to say this book is a must-read. It is really, really good. The scientific explanations are concise and distill what I'm sure are really complex processes into something digestible - and does a much better job of this than Siddhartha Mukherjee's book, in my opinion. The technology of gene editing is going to have some serious ramifications in perhaps the near future. Jennifer Doudna gives a future with gene-editing a thoughtful treatment and encourages us all to understand and be a part of the discussion, while trying a really exciting story of the technology's discovery and development to date.
December 4, 2021
استطاع مقص الجينات "كرسبر" من تحسين إنتاجنا الزراعي فصار عندنا أرز مقاوم للأمراض وطماطم تنضج بشكل أبطأ وفول صويا صحي غير مشبع بالدهون وبطاطس منخفضة السموم، فهل يستطيع كرسبر تعديل جينات البشر وتحسين جودة حياتنا وتصحيح أخطاء الحمض النووي ومنع حصول الأمراض وتصحيح الطفرات المرضية، أم أنه سيكون خطراً على مستقبلنا؟
الفايروسات القهقرية مثل فايروسات نقص المناعة البشرية تركت علامات على جنسنا البشري بحيث ان ٨٪ من الجينوم البشري هي من بقايا هذه الفايروسات القديمة التي أصابت أجدادنا.
العاثيات هي فايروسات قاتلة تطورت على مدى مليارات السنين وأصبحت ذات قدرة وحشية ضد البكتيريا التي قتلت منها أعداد هائلة، لم تقف البكتيريا عاجزة وطورت إنزيمات مهمتها تقطيع الأحماض النووية وتصحيح الأخطاء ومنع دخول الحمض النووي للعاثيات من دخول الخلية، بل واستطاعت نكران ذاتها وتفجير نفسها من أجل حماية المجتمع البكتيري الأكبر.
إحداث تغييرات في الخط الجرثومي البشري ليس مستحيلاً فنياً، لكن علينا دراسة أثر تلك التغييرات بدقة كبيرة، تنقيح جين CCR5 قد يُكسب الإنسان مناعة ضد فايروس نقص المناعة لكنه قد يجعله أكثر عرضة لفايروس حمى غرب النيل، وتعديل طفرات فقر الدم المنجلي قد تحرم الفرد من الحماية ضد الملاريا، لا نستطيع دائماً تقديم ضمانات ضد الأضرار الممكنة….
هناك مستقبل كبير ينتظر هذه التقنيات مع كثير من الأسئلة الأخلاقية التي يجب أن ينشغل بالإجابة عنها مفكرو المجتمعات المختلفة.
الفايروسات القهقرية مثل فايروسات نقص المناعة البشرية تركت علامات على جنسنا البشري بحيث ان ٨٪ من الجينوم البشري هي من بقايا هذه الفايروسات القديمة التي أصابت أجدادنا.
العاثيات هي فايروسات قاتلة تطورت على مدى مليارات السنين وأصبحت ذات قدرة وحشية ضد البكتيريا التي قتلت منها أعداد هائلة، لم تقف البكتيريا عاجزة وطورت إنزيمات مهمتها تقطيع الأحماض النووية وتصحيح الأخطاء ومنع دخول الحمض النووي للعاثيات من دخول الخلية، بل واستطاعت نكران ذاتها وتفجير نفسها من أجل حماية المجتمع البكتيري الأكبر.
إحداث تغييرات في الخط الجرثومي البشري ليس مستحيلاً فنياً، لكن علينا دراسة أثر تلك التغييرات بدقة كبيرة، تنقيح جين CCR5 قد يُكسب الإنسان مناعة ضد فايروس نقص المناعة لكنه قد يجعله أكثر عرضة لفايروس حمى غرب النيل، وتعديل طفرات فقر الدم المنجلي قد تحرم الفرد من الحماية ضد الملاريا، لا نستطيع دائماً تقديم ضمانات ضد الأضرار الممكنة….
هناك مستقبل كبير ينتظر هذه التقنيات مع كثير من الأسئلة الأخلاقية التي يجب أن ينشغل بالإجابة عنها مفكرو المجتمعات المختلفة.
July 31, 2023
Cele mai bune ilustrații pe care le-am văzut într-o carte de popularizare a științei -desene simple cu un stil aparte.
La sfârșitul lui 2012 se publică primul articol in Science care prezintă tehnologia CRISPR de editare genetică. Tehnici pentru editare genomului au existat de ani buni înainte de 2012 , dar lucru special la CRISPR este faptul că este simplu și IEFTIN.
CRISPR permite tratarea bolilor genetice dar este și o posibilă unealtă spre tratarea cancerului. Partea rea este editarea genomului uman și la dezavantaje sociale la care se poate ajunge -- super-oameni bogați și sclavi nemuritori.
Nu înțeleg de ce nu a fost tradusă cartea in română. Există biografia autoarei scrisă de un om care nu are legătură cu biochimia care a fost tradusă dar munca originală scrisă chiar de inventator se pierde in maculatura. Se traduc atâtea inutilității și se pierde esența.
La sfârșitul lui 2012 se publică primul articol in Science care prezintă tehnologia CRISPR de editare genetică. Tehnici pentru editare genomului au existat de ani buni înainte de 2012 , dar lucru special la CRISPR este faptul că este simplu și IEFTIN.
CRISPR permite tratarea bolilor genetice dar este și o posibilă unealtă spre tratarea cancerului. Partea rea este editarea genomului uman și la dezavantaje sociale la care se poate ajunge -- super-oameni bogați și sclavi nemuritori.
Nu înțeleg de ce nu a fost tradusă cartea in română. Există biografia autoarei scrisă de un om care nu are legătură cu biochimia care a fost tradusă dar munca originală scrisă chiar de inventator se pierde in maculatura. Se traduc atâtea inutilității și se pierde esența.
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