A Crack in Creation Summary and Review

by Jennifer A. Doudna, Samuel H. Sternberg

Has A Crack in Creation by Jennifer A. Doudna, Samuel H. Sternberg been sitting on your reading list? Pick up the key ideas in the book with this quick summary.

Can you imagine a world where genetic diseases, HIV or even cancer, could be cured simply by editing genes in your DNA? This may seem like just a fanciful idea, but it is an example of the wonderful possibilities gene editing could one day provide. Think this might be a far-off idea confined to sci-fi movies alone? Not true; we are lucky in that we may actually be alive when these procedures become standard practice in medicine. However, such an incredible leap forward in technology also has its potential for harm, just as with the nuclear bomb. Would we stop at just curing diseases? With a catalog of improved genes, such as offering better muscle development or increased intelligence gene editing could allow us to create “designer babies”. Of course, we would have to proceed with caution as this potential poses a myriad of ethical issues that humans, as a species, would have to work out. You’ll learn in this book summary,
  • How gene editing is poised to change our future 
  • How CRISPR could save your morning glass of OJ 
  • What startup was proposed to one of the authors

A Crack in Creation Key Idea #1: Genetic Modification: a natural process

Blossoming into an ornate display of biological diversity, life on Earth has evolved for billions of years through random genetic variations. Although this process has been understood through the Darwinian principles of evolution for many years, scientists are turning conventional theories of evolution upside down in the present day. a key player in the new age of biological mastery that is dawning, the author has made a decisive contribution to research enabling rational and intentional modifications of our genetic code – with no evolution necessary. It is important to understand is that cases of natural “gene editing” do occur so modifying the genetic code isn’t as unnatural as it might sound. In 2013, for example, National Institutes of Health, or NIH, scientists were perplexed by one of their patients.  The patient, Kim, suffered from a painful and potentially lethal immunodeficiency disorder called WHIM syndrome. WHIM is an obscure hereditary disease brought on by a single “spelling mistake” in human DNA code. Although Kim was diagnosed with WHIM in the 1960s, when scientists met with her again in 2013, she was miraculously symptom-free. Researchers studied Kim’s blood cells, where they found that in one of her chromosomes, an incredible 35 million letters were missing in her DNA code.  The rest of Kim’s DNA was also in complete disarray. Their only explanation for this apparent miracle was that a cell in Kim’s body had undergone a cataclysmic event in which a chromosome suddenly explodes, rearranging the genes it contains, known as chromothripsis. This disruption brought on a chain of events that erased the mistake causing her illness from Kim’s genetic code, which resulted in the total abatement of her symptoms. In this strange case, to the great benefit of her health, nature spontaneously and unintentionally “edited” Kim’s genome. Can you imagine if such corrections didn’t rely on the whims of nature or improbable flukes?  How amazing would it be if science could simply reverse any disastrous effects of genetic misspellings, correcting them and curing genetic disorders? This has been a question that has long been the topic of scientific debate.  

A Crack in Creation Key Idea #2: Deliberate Modifications: impractical until a new discovery.

It may be helpful to have a short refresher on the scientific language of this particular field before diving headfirst into the biological details of gene editing.  The complete set of genetic information contained within our cells is known as the genome.  All our physical characteristics such as height, skin color, even susceptibility to disease are determined by our genome. DNA, or deoxyribonucleic acid, makes up the genome.  This complex is composed of four different chemical groups: adenine, (A); guanine, (G); cytosine, (C); and thymine, (T). Therefore, A, G, C, and T are the four letters of the genetic alphabet. The human genome is then divided into 26 packages of DNA known as chromosomes. Genes are smaller groups within chromosomes and are sections of DNA responsible for specific bodily functions. Now that the terminology lesson out is of the way, we can get back to the subject of gene editing.  The long search for a way to modify the genetic code all began when scientists with a virus.  Scientists observed that viruses could actually insert their own DNA into host cells. Even more amazing, it is possible for viruses to weave their genome into a bacterial chromosome. Gene editing made its first breakthrough from this vital observation.  In the 1980s, researchers Mario Capecchi and Oliver Smithies, through a process known as homologous recombination, succeeded in replacing defective genes with intact genes. The technique was only successful in one out of 100 attempts, so, unfortunately, it had no therapeutic viability.  Other techniques were developed during the 1990s and 2000s.  These, as well, were impractical in clinical application as they were plagued by extreme complexity. This changed when researchers discovered a region of bacterial DNA that they dubbed clustered regularly interspaced short palindromic repeats, or CRISPR.  To an ordinary person, this means the DNA repeated itself exactly over certain intervals. The discovery of CRISPR led to the development of a technique both simple and effective enough to actually be used in the real world.  

A Crack in Creation Key Idea #3:  Paving the Way: a DNA cutting machine

Now that you know that CRISPRs are the key to effective gene editing, you may ask yourself - what exactly are they? Quite simply, CRISPRs are regions of bacterial DNA in which the genetic sequences are replicated exactly. Between the repetitions, scientists found spacer sequences, similarly-sized lines of DNA. Quite common in the DNA of bacteria, genetic peculiarities like CRISPRs tend to pop up frequently when nature has an important function for them.  When they noticed that the spacer sequences within CRISPRs perfectly match the DNA of bacterial viruses, scientists in the mid-2000s came closer to deciphering what exactly this function was. It didn’t take long for geneticists to realize that CRISPR DNA is central to the bacterial immune system, which is responsible for fighting off viruses. By recording memories of past viruses as spacer sequences in CRISPR DNA, bacteria, CRISPRs function sort of like molecular “vaccination cards. The CRISPRs enable bacteria to recognize and destroy viruses very quickly during future infections. To accomplish this, CRISPR sequences use three essential components to cut through the virus DNA. First are the CRISPR-associated, or CAS, genes. Most important among them is the Cas9 gene, which codes for a special protein that disassembles and disables invading DNA. These genes reside in the regions adjacent to CRISPR DNA. The second component is the CRISPR RNA.  RNA, or ribonucleic acid, is DNA’s cousin. RNA is created from DNA by swapping out the letter T of thymine for the U of uracil. CRISPR RNA acts as a messenger within cells to guide the Cas9 protein to the location where a snip is needed on the strand. And finally, helping to activate the cutting process, tracrRNA plays the role of a surgical assistant. Looking at their findings, the next logical question for researchers was: if CRISPRs can help bacteria cut viral DNA, could they be used in a lab to target and splice other DNA?  

A Crack in Creation Key Idea #4: Using CRISPR: a cheap and easy method for gene editing

Now you know about how gene cuts are made using CRISPR, but there are still many technical concepts and terms to learn. Here’s a quick recap: The CRISPR RNA, when given a piece of CRISPR DNA associated with this genetic sequence can guide the cutting Cas9 gene protein to a specific location in foreign DNA. The location was determined because it precisely matches one of the spacer sequences in the original CRISPR DNA. The Cas9 protein cuts out the matching piece and is led away by its guide RNA when its work is done. Then the cut piece DNA begins to try to mend itself through the body’s natural repair mechanisms.  There is a brief window during which scientists can insert a different piece of DNA into the gap before natural repair begins.  It is in this way, the author was the first to demonstrate how CRISPRs can be utilized as an effective gene-editing tool. The author, in a groundbreaking 2012 paper coauthored with Emmanuelle Charpentier and published in the journal Science, demonstrated how the CRISPR gene editing method could be applied to this end. The paper discussed how the pair, at specific and deliberate locations, sliced jellyfish DNA apart. While this operation alone constituted a major breakthrough in the field, the fact that it was remarkably cheap and easy to use made the CRISPR method even more incredible. Their methods and results aroused great excitement in the scientific community and inspired further research. A Harvard professor Kiran Musunuru applied the method to the DNA of patients suffering from a genetic disease that deforms red blood cells and makes it difficult for them to transport oxygen through the body called sickle cell anemia. Sickle cell anemia is caused by a single-letter mutation in the beta-globin gene.  Musunuru corrected this catastrophic misspelling in his laboratory by applying the CRISPR method. In an instant, CRISPR became a most valuable tool in genetic research as such an ability to change DNA holds the potential to transform medicine.  

A Crack in Creation Key Idea #5: Agriculture: gene editing has a number of practical applications

The discovery of the CRISPR gene editing method has opened up a whole new world of opportunities in gene therapy.   The exciting prospect of controlling the human genome has removed the limits of human imagination in gene engineering. Would it be possible for scientists to make woolly mammoths or unicorns? While such ideas do present themselves to the minds of prominent gene thinkers, there are certainly much more practical applications for gene manipulation.   In agriculture, for example, gene editing tools could be used to create more resilient crops, higher yields, and healthier food. The citrus industry is currently suffering from a bacterial plant disease known as huanglongbing, or yellow dragon disease when translated from Chinese. This infection threatens the orchards of Florida and California after decimating plantations in Asia.  CRISPR could be used to create quickly create plants resistant to the bacteria. We could even use CRISPR to make food healthier for us.  Even though we consume millions of tons of soybean oil every year, this oil has been linked to elevated cholesterol and heart disease because it contains unhealthy levels of trans fats.  Soybean genetics could be altered using CRISPR, reducing the unhealthy fatty acids present in this freely available food. Gene editing isn’t confined to plants. Gene editing could be applied to livestock in many ways as well.  The “Enviropig, produced by Canadian researchers is a genetically modified sow.  This pig has had a gene from the E. Coli bacteria added to its DNA to improve its digestion, resulting in a 75-percent reduction in the phosphorous content of its manure. Since phosphorous-laden manure can its way into streams and rivers and encourage algal blooms that kill aquatic life, this is a significant environmental development. Another potential application for similar gene manipulation is seen in cows. The horns of cows are often removed for safety during transport.  This process can cause pain and stress to the animal.  If we simply design a cow that never grows horns in the first place this trauma could be avoided entirely.  

A Crack in Creation Key Idea #6: A New World: CRISPR gene editing and medical possibilities

There are more than 7,000 human genetic diseases that are each caused by the mutation of just a single gene. This may seem shocking, but fortunately, CRISPRs can now be used to identify cures for many of these illnesses.  With this affordable, easy-to-use genetic editing tool at our fingertips, we may soon see the use of precise genetic therapies, ushering in a new era of medicine. A case in point is HIV, the human immunodeficiency virus, a sexually transmitted disease that afflicts millions of people globally. You might not know this, but there are some lucky people with natural resistance to HIV resulting from a mutation in the CCR5 gene, which codes for a specific protein. Current research strongly indicates that it could be possible to prevent HIV infection in the first place by using CRISPR to edit the CCR5 gene into nonresistant subjects. Another disease that may benefit from CRISPR technology is Duchenne muscular dystrophy, or DMD, a fatal muscle-degenerative disease. This genetic disease is inherited by one in 3,600 male babies. Those who suffer from the disorder often end up in a wheelchair by the age of ten because they experience severe muscular degeneration. The mutation of a single gene; in this case, the so-called DMD gene causes this disease.  It has been indicated by recent studies conducted on mice that CRISPR could help find a cure. Due to the opportunities opened up by CRISPR gene editing, cancer research could experience a leap forward as well. After all, we know cancer is caused by DNA mutations, some of which are acquired through habits such as smoking and others inherited.  CRISPR could offer new treatments to eliminate such mutations, perhaps preventing cancer altogether. While it is clear to us that gene editing has much to offer, being in total control of our genes, and with that our evolution, is an extremely complex matter. This exciting breakthrough also comes with numerous risks.  

A Crack in Creation Key Idea #7: Ethical Questions: gene editing requires careful discussion

Only two years after the author and her colleague made their breakthrough discovery, public excitement about CRISPR was on the rise in 2014. It was around this same time, Samuel Sternberg, a Ph.D. student of the author’s, was approached with an offer by an up-and-coming entrepreneur to join a start-up  company offering couples the first “CRISPR baby.” Even though Sternberg declined the proposition, it raised serious ethical questions nonetheless. Some felt gene editing had become too easy and accessible. What exactly is at stake with the development of this technology? By curing or preventing genetic diseases, gene editing using CRISPR can undoubtedly do a world of good.  But what about something like offering “designer babies?” What are the ethical ramifications of using CRISPR to choose a baby’s gender or add genes associated with desirable characteristics like blue eyes or intelligence? The author’s concern was CRISPR’s potential for being abused. Her fear increased so much that in a dream she met Adolf Hitler.  The former dictator asked her for details of CRISPR.  This made her think about what would have happened if her discovery had been used by the genocidal maniac to meticulously create a genetically filtered Aryan race. The plain fact is, there are a great many difficult questions just like these to ponder, and an open discussion about gene editing is the only solution. Discussing the ethical implications of gene editing in both the scientific community and society at large was the aim of the author along with several other experts in the field when they published a white paper in 2015. The paper more specifically focused on gene editing in the cells that pass on genetic information, known as the human germline. The scientific community was urged by this paper to defer this line of research until after a comprehensive discussion about the social, ethical and philosophical dilemmas involved could take place. It is vital that the decision about how to use CRISPR be made by human society at large.  However; to make such an important decision, people first need to be educated on the matter.  

A Crack in Creation Key Idea #8: The Future: gene editing hinges on a number of considerations

We know there’s a lot of deliberation that needs to take place before gene editing moves forward.  In the present debate, there are a few contending opinions. Tene editing of human embryos is a good example. While in accordance with directives from the Barack Obama administration. the National Institutes of Health called for the suspension of all research involving this field, others feel that this research should be pursued aggressively. While this is certainly complicated terrain, for the author, there are three general themes to consider before any decisions can be made on whether human gene-editing should be pursued: safety, ethics , and regulation. The author believes that, sooner or later, germline editing will be safe enough for clinical use. Even if the CRISPR procedure produced unintended mutations, the overall benefits of eliminating disease-causing genes would likely outweigh the dangers.  After all, the human body experiences around 1 million natural genetic mutations every second on its own. The ethical dimension is important because once we have tools to safely correct disease-causing mutations, there will be a strong argument to use them. Yet there’s a thin and potentially dangerous line between simply improving people’s health and producing genetic enhancements to desirable characteristics like intelligence, athleticism, or beauty. With the latter approach, it would be the wealthy who would benefit most from germline editing, which only they will be able to afford. Despite the legitimacy of these objections, there shouldn’t be a general prohibition on germline editing. Regulations are the final considerations to be made. Governments, each tasked with representing their societies, must play a key role in overseeing the methods used in the modification of the human germline. Ideally, a global consensus could be reached on how such policies are written and applied. If you’re impatient to benefit from this brave new world, don’t worry, steps are already being taken in that direction. In 2015, the International Summit on Human Gene Editing was attended by many politicians and scientists alike. These events create the space necessary for these important conversations to unfold, so they will no doubt become more common in the future,

In Review: 

Scientists have learned by taking cues from nature that the human genome can be edited through a process called CRISPR. Whether it should be edited is not so clear. Humans have reached a point where major genetic interventions are possible and medical science must now carefully consider the ramifications of this ability.