Category Archives: Genetic Engineering

Genetic engineering is the process of altering the genetic composition of plants, animals, and humans. The most practical application of genetic engineering is to create a more sustainable food system for the people of Earth, but there are other ways we can use it to our advantage as well.

Unfortunately, there are both pros and cons of genetic engineering. For every benefit, there is a list of concerns and potential problems we need to consider. There is a substantive argument on both sides of genetic engineering, and well explore both ahead.

Most people tend to focus on the negatives of genetic engineering, but there are some substantial positive we need to consider as well. Genetic engineering is a debate, and there are some good points on each side. You have to look at both the pros and cons of genetic engineering if you want to make an informed decision on the matter.

Evolution takes thousands of years to adapt to our surroundings, but genetic engineering offers a quicker path forward. With the assistance of genetic engineering, we could force our bodies to adapt to the changing climate of our planet.

Additionally, we could tack-on some extra years to our lives by altering our cells, so our bodies dont deteriorate as quickly as they currently do. The fountain of youth might be within our reach, and many look forward to advancements in the area of genetic engineering.

If we choose to go down this path, well feel better as we age and be able to outlast some of the diseases that currently take us down. We still wont be able to live forever, but genetic engineering shows promise in extending the prime of our lives.

Food shortage is a massive problem in the world, especially with the growing population. Were destroying natural habitats to make way for farmland, and overgrazing is causing current pastures to become dry and uninhabited.

The answer to this problem could come in the form of genetic engineering. If we can alter the composition of vegetables and animals, we can create new foods that might have more nutritional value than nature creates on its own.

We might even be able to advance to a point where foods give us medicines we need to combat widespread viruses and illnesses. Food is one of the most promising spaces when considering the prospect of genetic engineering.

A lot of diseases depend on genetic predisposition. Some people are more likely to get cancer, Alzheimers and other diseases than their neighbor. With genetic engineering, we can get rid of these genetic predispositions once and for all.

There will likely still be some environmental concerns that will cause diseases, but if we start altering the genes of humans, we may become resistant to genetic abnormalities. Family history wont mean anything when it comes to things like cancer, and we can start eliminating diseases that are completely based on genetics.

There are already a handful of diseases and illnesses we can detect while a baby is still in the womb. We even can genetically engineer some diseases and illnesses out of a babys system before theyre born.

Finding out your baby has a disease can be devastating, and some parents make the difficult choice to spare their child possible pain. If you know that your baby might suffer and die a few months after theyre born, you have to decide whether or not you want to roll the dice.

In the future, we might be able to eliminate the chances of unhealthy babies. Diseases like Huntingtons offer a substantial chance that the carrier will pass it onto their child. If the child isnt positive for the disease, theyll still be a carrier and have to deal with the same dilemma when it comes time to have kids of their own.

Genetic engineering has the potential to stop these threats in their tracks. Parents wont have to worry about birthing a healthy son or daughter. Science will guarantee that every baby is happy and healthy when they come into this world.

Of course, genetic engineering isnt entirely positive. There is an upside to the ability to genetically alter humans and animals, but only in ideal situations.

Our world isnt perfect, and scientists make mistakes all the time. We cant assume that genetic engineering will be available to the entirety of the human population, which is a flaw in itself.

The negatives of genetic engineering seem to outweigh the positives, especially since there is so much room for error. We dont know what were tampering with, which opens the door to a host of potential problems.

There are a couple of ethical problems with genetic engineering that we need to consider as a society. Those who subscribe to religion will see genetic engineering as blasphemy, for instance. Wed be playing God, in a sense. Anyone who believes in creation will be expressly against genetic engineering especially in human children.

Those who are on the opposite side of the spectrum from religious people probably wont love genetic engineering either. Genetically engineered food might work, but changing the genes of people will add to the overpopulation problem were currently experiencing.

Diseases are one of the most effective forms of population control. We dont have the heart to eliminate other humans in the name of population control, so disease does it for us. If we eliminate diseases, humans will have virtually no threat left on this planet.

Living longer lives might be ideal, but it isnt practical. If we extend the prime of our lives, were opening the door to having more children. Since all children would be in perfect health, well see a population increase that could have devastating consequences.

If genetic engineering becomes a reality, it will likely only be available to the richest members of society. Theyll be able to extend their lives, limit diseases, and make sure their children are always healthy when theyre born

When this happens, natural selection is completely obsolete. Instead, the wealthiest in society will thrive while the poor will die-out. Eventually, genetic diversity will completely disappear as genetically engineered children all express the most desirable characteristics

This problem also arises in nature if we decide to engineer plants and animals genetically. These organisms might start as food, but could introduce themselves to the wild and take over. Theyll decimate natural species, and eventually be the only thing left.

One of the biggest hurdles in genetic engineering is the possibility of errors or genetic defects, especially in humans. Scientists have a general understanding of what creates a functioning human, but they dont yet have all the pieces to the puzzle.

When it comes down to changing humans at a cellular level, scientists dont yet have the understanding of how small changes can affect the development of a growing baby. Changing genes could result in more damaging birth defects or even miscarriages.

Furthermore, tampering with diseases could end up creating a super-disease that is even harder to combat. There are too many variables in the human body for genetic engineering to work to the fullest potential. Even if it could, people will probably be too nervous to trust scientists tampering with the cells of their future children.

Science still isnt at a point where they can alter the genes of humans to prevent all diseases in unborn children, but it might be there soon. When that time comes, some might take genetic engineering to its logical extreme.

Our priority will be to create healthy children. Once we perfect this process, though, where to, we go? The next logical step is the ability to pick certain traits that our children will have. We might be able to select whether we have a boy or girl. Then, we can decide what eye color and hair color they have.

Pretty soon, were selecting every trait that our child has before they leave the womb. Nature will be virtually out of the question at this point, and people with enough money will design their babies from scratch.

Since the pros and cons of genetic engineering are compelling, its worth it to explore the possibility further. We still havent reached a place where scientists fully understand the opportunities genetic engineering presents, so they still have years of research on their hands.

In the end, though, no system of genetically altering humans, animals, or plants will be perfect. There is a massive potential for errors, and we likely wont have equal opportunities if and when scientists ever crack the case.

Although the positives of genetic engineering are convincing, the negatives can be terrifying. If we ever get to the point where we can genetically alter humans, we need to consider the moral, ethical, and practical application of technology before going any further.

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Pros and Cons of Genetic Engineering - Benefits and Risks

Genetic engineering, also calledgenetic modification, is the direct manipulation of an organismsgenomeusing biotechnology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novelorganisms. Read important facts about Genetic Engineering in this article for the IAS Exam.

NewDNAmay be inserted in the host genome by first isolating and copying the genetic material of interest usingmolecular cloningmethods to generate a DNA sequence, or by synthesizing the DNA and then inserting this construct into the host organism.Genesmay be removed, or knocked out, using anuclease.Gene targetingis a different technique that useshomologous recombinationto change an endogenous gene and can be used to delete a gene, removeexons, add a gene, or introducepoint mutations.

Aspirants reading, GEAC can also refer to topics lined below:

Medicine, research, industry and agriculture are a few sectors where genetic engineering applies. It can be used on various plants, animals and microorganisms. The first microorganism to be genetically modified is bacteria.

Genetic Engineering Appraisal Committee (GEAC) is the biotech regulator in India. It is created under the Ministry of Environment and Forests. Read more about GEAC in the linked article.

There are five bodies that are authorized to handle rules noted underEnvironment Protection Act 1986 Rules for Manufacture, Use, Import, Export and Storage of Hazardous Microorganisms/Genetically Engineered Organisms or Cells 1989. These are:

Soybean-Herbicide tolerance,Canola-Altered fatty acid composition,Plum-Virus resistance,Corn-Insect resistance

Pros:Tackling and Defeating Diseases,Getting Rid of All Illnesses in Young and Unborn Children,Potential to Live Longer,Produce New Foods,Faster Growth in Animals and Plants,Pest and Disease Resistance.Cons:May Lead to Genetic Defects,Limits Genetic Diversity,Reduced Nutritional Value,Risky Pathogens,Negative Side Effects

UPSC Preparation:

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Genetic Engineering - Meaning, Applications, Advantages and Challenges ...

Genetic engineering is the alteration of an organisms genotype using recombinant DNA technology to modify an organisms DNA to achieve desirable traits. The addition of foreign DNA in the form of recombinant DNA vectors generated by molecular cloning is the most common method of genetic engineering. The organism that receives the recombinant DNA is called a genetically modified organism (GMO). If the foreign DNA that is introduced comes from a different species, the host organism is called transgenic. Bacteria, plants, and animals have been genetically modified since the early 1970s for academic, medical, agricultural, and industrial purposes. In the US, GMOs such as Roundup-ready soybeans and borer-resistant corn are part of many common processed foods.

Although classical methods of studying the function of genes began with a given phenotype and determined the genetic basis of that phenotype, modern techniques allow researchers to start at the DNA sequence level and ask: What does this gene or DNA element do? This technique, called reverse genetics, has resulted in reversing the classic genetic methodology. This method would be similar to damaging a body part to determine its function. An insect that loses a wing cannot fly, which means that the function of the wing is flight. The classical genetic method would compare insects that cannot fly with insects that can fly, and observe that the non-flying insects have lost wings. Similarly, mutating or deleting genes provides researchers with clues about gene function. The methods used to disable gene function are collectively called gene targeting. Gene targeting is the use of recombinant DNA vectors to alter the expression of a particular gene, either by introducing mutations in a gene, or by eliminating the expression of a certain gene by deleting a part or all of the gene sequence from the genome of an organism.

The process of testing for suspected genetic defects before administering treatment is called genetic diagnosis by genetic testing. Depending on the inheritance patterns of a disease-causing gene, family members are advised to undergo genetic testing. For example, women diagnosed with breast cancer are usually advised to have a biopsy so that the medical team can determine the genetic basis of cancer development. Treatment plans are based on the findings of genetic tests that determine the type of cancer. If the cancer is caused by inherited gene mutations, other female relatives are also advised to undergo genetic testing and periodic screening for breast cancer. Genetic testing is also offered for fetuses (or embryos with in vitro fertilization) to determine the presence or absence of disease-causing genes in families with specific debilitating diseases.

Gene therapy is a genetic engineering technique used to cure disease. In its simplest form, it involves the introduction of a good gene at a random location in the genome to aid the cure of a disease that is caused by a mutated gene. The good gene is usually introduced into diseased cells as part of a vector transmitted by a virus that can infect the host cell and deliver the foreign DNA (Figure 1). More advanced forms of gene therapy try to correct the mutation at the original site in the genome, such as is the case with treatment of severe combined immunodeficiency (SCID).

Traditional vaccination strategies use weakened or inactive forms of microorganisms to mount the initial immune response. Modern techniques use the genes of microorganisms cloned into vectors to mass produce the desired antigen. The antigen is then introduced into the body to stimulate the primary immune response and trigger immune memory. Genes cloned from the influenza virus have been used to combat the constantly changing strains of this virus.

Antibiotics are a biotechnological product. They are naturally produced by microorganisms, such as fungi, to attain an advantage over bacterial populations. Antibiotics are produced on a large scale by cultivating and manipulating fungal cells.

Recombinant DNA technology was used to produce large-scale quantities of human insulin in E. coli as early as 1978. Previously, it was only possible to treat diabetes with pig insulin, which caused allergic reactions in humans because of differences in the gene product. Currently, the vast majority of diabetes suffers who inject insulin do so with insulin produced by bacteria.

Human growth hormone (HGH) is used to treat growth disorders in children. The HGH gene was cloned from a cDNA library and inserted into E. coli cells by cloning it into a bacterial vector. Bacterial HGH can be used in humans to reduce symptoms of various growth disorders.

Although several recombinant proteins used in medicine are successfully produced in bacteria, some proteins require a eukaryotic animal host for proper processing. For this reason, the desired genes are cloned and expressed in animals, such as sheep, goats, chickens, and mice. Animals that have been modified to express recombinant DNA are called transgenic animals. Several human proteins are expressed in the milk of transgenic sheep and goats, and some are expressed in the eggs of chickens. Mice have been used extensively for expressing and studying the effects of recombinant genes and mutations.

Manipulating the DNA of plants (i.e., creating GMOs) has helped to create desirable traits, such as disease resistance, herbicide and pesticide resistance, better nutritional value, and better shelf-life (Figure 3). Plants are the most important source of food for the human population. Farmers developed ways to select for plant varieties with desirable traits long before modern-day biotechnology practices were established.

Plants that have received recombinant DNA from other species are called transgenic plants. Because they are not natural, transgenic plants and other GMOs are closely monitored by government agencies to ensure that they are fit for human consumption and do not endanger other plant and animal life. Because foreign genes can spread to other species in the environment, extensive testing is required to ensure ecological stability. Staples like corn, potatoes, and tomatoes were the first crop plants to be genetically engineered.

Gene transfer occurs naturally between species in microbial populations. Many viruses that cause human diseases, such as cancer, act by incorporating their DNA into the human genome. In plants, tumors caused by the bacterium Agrobacterium tumefaciens occur by transfer of DNA from the bacterium to the plant. Although the tumors do not kill the plants, they make the plants stunted and more susceptible to harsh environmental conditions. Many plants, such as walnuts, grapes, nut trees, and beets, are affected by A. tumefaciens. The artificial introduction of DNA into plant cells is more challenging than in animal cells because of the thick plant cell wall.

Researchers used the natural transfer of DNA from Agrobacterium to a plant host to introduce DNA fragments of their choice into plant hosts. In nature, the disease-causing A. tumefaciens have a set of plasmids, called the Ti plasmids (tumor-inducing plasmids), that contain genes for the production of tumors in plants. DNA from the Ti plasmid integrates into the infected plant cells genome. Researchers manipulate the Ti plasmids to remove the tumor-causing genes and insert the desired DNA fragment for transfer into the plant genome. The Ti plasmids carry antibiotic resistance genes to aid selection and can be propagated in E. coli cells as well.

Bacillus thuringiensis (Bt) is a bacterium that produces protein crystals during sporulation that are toxic to many insect species that affect plants. Bt toxin has to be ingested by insects for the toxin to be activated. Insects that have eaten Bt toxin stop feeding on the plants within a few hours. After the toxin is activated in the intestines of the insects, death occurs within a couple of days. Modern biotechnology has allowed plants to encode their own crystal Bt toxin that acts against insects. The crystal toxin genes have been cloned from Bt and introduced into plants. Bt toxin has been found to be safe for the environment, non-toxic to humans and other mammals, and is approved for use by organic farmers as a natural insecticide.

The first GM crop to be introduced into the market was the Flavr Savr Tomato produced in 1994. Antisense RNA technology was used to slow down the process of softening and rotting caused by fungal infections, which led to increased shelf life of the GM tomatoes. Additional genetic modification improved the flavor of this tomato. The Flavr Savr tomato did not successfully stay in the market because of problems maintaining and shipping the crop.

Unless otherwise noted, images on this page are licensed under CC-BY 4.0 by OpenStax.

OpenStax, Biology. OpenStax CNX. May 27, 2016 http://cnx.org/contents/s8Hh0oOc@9.10:8CA_YwJq@3/Cloning-and-Genetic-Engineerin

Moen I, Jevne C, Kalland K-H, Chekenya M, Akslen LA, Sleire L, Enger P, Reed RK, Oyan AM, Stuhr LEB. 2012.Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation.BMC Cancer. 12:21. doi:10.1186/1471-2407-12-21 PDF

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Genetic Engineering Principles of Biology

Indeed, some people are adamant that germ-line engineering is being pushed ahead with false arguments. That is the view of Edward Lanphier, CEO of Sangamo Biosciences, a California biotechnology company that is using another gene-editing technique, called zinc fingers nucleases, to try to treat HIV in adults by altering their blood cells. Weve looked at [germ-line engineering] for a disease rationale, and there is none, he says. You can do it. But there really isnt a medical reason. People say, well, we dont want children born with this, or born with thatbut its a completely false argument and a slippery slope toward much more unacceptable uses.

Critics cite a host of fears. Children would be the subject of experiments. Parents would be influenced by genetic advertising from IVF clinics. Germ-line engineering would encourage the spread of allegedly superior traits. And it would affect people not yet born, without their being able to agree to it. The American Medical Association, for instance, holds that germ-line engineering shouldnt be done at this time because it affects the welfare of future generations and could cause unpredictable and irreversible results. But like a lot of official statements that forbid changing the genome, the AMAs, which was last updated in 1996, predates todays technology. A lot of people just agreed to these statements, says Greely. It wasnt hard to renounce something that you couldnt do.

The fear? A dystopia of superpeople and designer babies for those who can afford it.

Others predict that hard-to-oppose medical uses will be identified. A couple with several genetic diseases at once might not be able to find a suitable embryo. Treating infertility is another possibility. Some men dont produce any sperm, a condition called azoospermia. One cause is a genetic defect in which a region of about one million to six million DNA letters is missing from the Y chromosome. It might be possible to take a skin cell from such a man, turn it into a stem cell, repair the DNA, and then make sperm, says Werner Neuhausser, a young Austrian doctor who splits his time between the Boston IVF fertility-clinic network and Harvards Stem Cell Institute. That will change medicine forever, right? You could cure infertility, that is for sure, he says.

I spoke with Church several times by telephone over the last few months, and he told me whats driving everything is the incredible specificity of CRISPR. Although not all the details have been worked out, he thinks the technology could replace DNA letters essentially without side effects. He says this is what makes it tempting to use. Church says his laboratory is focused mostly on experiments in engineering animals. He added that his lab would not make or edit human embryos, calling such a step not our style.

What is Churchs style is human enhancement. And hes been making a broad case that CRISPR can do more than eliminate disease genes. It can lead to augmentation. At meetings, some involving groups of transhumanists interested in next steps for human evolution, Church likes to show a slide on which he lists naturally occurring variants of around 10 genes that, when people are born with them, confer extraordinary qualities or resistance to disease. One makes your bones so hard theyll break a surgical drill. Another drastically cuts the risk of heart attacks. And a variant of the gene for the amyloid precursor protein, or APP, was found by Icelandic researchers to protect against Alzheimers. People with it never get dementia and remain sharp into old age.

Church thinks CRISPR could be used to provide people with favorable versions of genes, making DNA edits that would act as vaccines against some of the most common diseases we face today. Although he told me anything edgy should be done only to adults who can consent, its obvious to him that the earlier such interventions occur, the better.

Church tends to dodge questions about genetically modified babies. The idea of improving the human species has always had enormously bad press, he wrote in the introduction to Regenesis, his 2012 book on synthetic biology, whose cover was a painting by Eustache Le Sueur of a bearded God creating the world. But thats ultimately what hes suggesting: enhancements in the form of protective genes. An argument will be made that the ultimate prevention is that the earlier you go, the better the prevention, he told an audience at MITs Media Lab last spring. I do think its the ultimate preventive, if we get to the point where its very inexpensive, extremely safe, and very predictable. Church, who has a less cautious side, proceeded to tell the audience that he thought changing genes is going to get to the point where its like you are doing the equivalent of cosmetic surgery.

Some thinkers have concluded that we should not pass up the chance to make improvements to our species. The human genome is not perfect, says John Harris, a bioethicist at Manchester University, in the U.K. Its ethically imperative to positively support this technology. By some measures, U.S. public opinion is not particularly negative toward the idea. A Pew Research survey carried out last August found that 46 percent of adults approved of genetic modification of babies to reduce the risk of serious diseases.

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Engineering the Perfect Baby | MIT Technology Review

What is CRISPR?

CRISPR is a powerful tool for editing genomes, meaning it allows researchers to easily alter DNA sequences and modify gene function. It has many potential applications, including correcting genetic defects, treating and preventing the spread of diseases, and improving the growth and resilience of crops. However, despite its promise, the technology also raises ethical concerns.

In popular usage, "CRISPR" (pronounced "crisper") is shorthand for "CRISPR-Cas9." CRISPRs are specialized stretches of DNA, and the protein Cas9 where Cas stands for "CRISPR-associated" is an enzyme that acts like a pair of molecular scissors, capable of cutting strands of DNA.

CRISPR technology was adapted from the natural defense mechanisms of bacteria and archaea, a domain of relatively simple single-celled microorganisms. These organisms use CRISPR-derived RNA, a molecular cousin to DNA, and various Cas proteins to foil attacks by viruses. To foil attacks, the organisms chop up the DNA of viruses and then stow bits of that DNA in their own genome, to be used as a weapon against the foreign invaders should those viruses attack again.

When the components of CRISPR are transferred into other, more complex, organisms, those components can then manipulate genes, a process called "gene editing." No one really knew what this process looked like until 2017, when a team of researchers led by Mikihiro Shibata of Kanazawa University in Japan and Hiroshi Nishimasu of the University of Tokyo showed, for the very first time, what it looks like when a CRISPR is in action, Live Science previously reported.

Related: Genetics by the numbers: 10 tantalizing tales

CRISPRs: The term "CRISPR" stands for "clusters of regularly interspaced short palindromic repeats" and describes a region of DNA made up of short, repeated sequences with so-called "spacers" sandwiched between each repeat.

When we talk about repeats in the genetic code, we're talking about the ordering of rungs within the spiral ladder of a DNA molecule. Each rung contains two chemical bases bound together: A base called adenine (A) links up to another called thymine (T), and the base guanine (G) pairs with cytosine (C).

In a CRISPR region, these bases appear in the same order several times, and in these repeated segments, they form what's known as "palindromic" sequences, according to the Max Planck Institute. A palindrome, like the word "racecar," reads the same forward as it does backward; similarly, in a palindromic sequence, bases on one side of the DNA ladder match those on the opposing side when you read them in opposite directions.

For example, a super simple palindromic sequence might look like this:

Short palindromic repeats appear throughout CRISPR regions of DNA, with each repeat bookended by "spacers." Bacteria swipe such spacers from viruses that have attacked them, meaning they incorporate a bit of viral DNA into their own genome. These spacers serve as a bank of memories, which enables the bacteria to recognize the viruses if they should ever attack again. You can also think of spacers like "Wanted" posters, providing a snapshot of the bad guys so they can be easily spotted and brought to justice.

Related: Going viral: 6 new findings about viruses

Rodolphe Barrangou and a team of researchers at Danisco, a food ingredients company, first demonstrated this process experimentally. In a 2007 paper published in the journal Science, the researchers used Streptococcus thermophilus bacteria, which are commonly found in yogurt and other dairy cultures, as their model, according to the Joint Genome Institute, part of the U.S. Department of Energy. They observed that after a viral attack, the bacteria incorporated new spacers into their CRISPR regions. Moreover, the DNA sequence of these spacers was identical to parts of the virus genome.

The team also manipulated the spacers by removing them and inserting new viral DNA sequences in their place. In this way, the researchers were able to alter the bacteria's resistance to an attack by a specific virus, confirming CRISPRs' role in regulating bacterial immunity.

CRISPR RNA (crRNA): CRISPR regions of DNA act as a kind of bank of viral memories; but for that stored information to be useful elsewhere in the cell, it must be copied, or "transcribed," into a different genetic molecule called RNA. Unlike DNA sequences, which remain lodged inside the DNA molecule, this CRISPR RNA (crRNA) can roam about the cell and team up with proteins namely the molecular scissors that snip viruses to bits.

RNA also differs from DNA in that it's only one strand, rather than two, meaning it looks like just a half of a ladder. To build an RNA molecule, one part of the CRISPR acts as a template and proteins called polymerases swoop in to construct an RNA molecule that is "complementary" to that template, meaning the two strands' bases would fit together like puzzle pieces. For example, a G in the DNA molecule would get transcribed as a C in the RNA.

Each snippet of CRISPR RNA contains a copy of a repeat and a spacer from a CRISPR region of DNA, according to a 2014 review by Jennifer Doudna and Emmanuelle Charpentier, published in the journal Science. The crRNA interacts with the Cas9 protein and another kind of RNA, called "trans-activating crRNA" or tracrRNA, in order to help bacteria fend off viruses.

Cas9: The Cas9 protein is an enzyme that cuts foreign DNA. The protein binds to crRNA and tracrRNA, which together guide Cas9 to a target site on the virus's DNA strand where the protein will make its cut. The target DNA that the Cas9 will cut through is complementary to a 20-nucleotide stretch of the crRNA, where a "nucleotide" is a building block of DNA that contains one base.

Using two separate regions or "domains" on its structure, Cas9 cuts both strands of the DNA double helix, making what is known as a "double-stranded break," according to the 2014 Science article.

There is a built-in safety mechanism that ensures that Cas9 doesn't just cut just anywhere in a genome. Short DNA sequences known as "protospacer adjacent motifs," or PAMs, serve as tags and sit adjacent to the target DNA sequence. If the Cas9 complex doesn't see a PAM next to its target DNA sequence, it won't cut. This is one possible reason that Cas9 doesn't ever attack the CRISPR region in bacteria, according to a 2014 review published in Nature Biotechnology (opens in new tab).

Genomes encode a series of messages and instructions within their DNA sequences, and genome editing involves changing those sequences, thereby changing the messages they contain. This can be done by inserting a cut or break in the DNA and tricking a cell's natural DNA repair mechanisms into introducing the targeted changes. CRISPR-Cas9 provides a means to do so.

In 2012, two pivotal research papers were published in the journals Science and PNAS, describing how the bacterial CRISPR-Cas9 could be used to chop up any DNA, not just that of viruses. In this way, the natural CRISPR system could be transformed into a simple, programmable genome-editing tool.

To direct Cas9 to snip a specific region of DNA, scientists can simply change the sequence of the crRNA, which binds to a complementary sequence in the target DNA, the studies concluded.In the 2012 Science article, Martin Jinek and his colleagues further simplified the system by fusing crRNA and tracrRNA to create a single "guide RNA." Thus, genome editing requires only two components: a guide RNA and the Cas9 protein.

"Operationally, you design a stretch of 20 base pairs that match a gene that you want to edit," and from there, one can figure out what the complementary crRNA sequence would be, George Church, a professor of genetics at Harvard Medical School, told Live Science. Church emphasized the importance of making sure that the nucleotide sequence is found only in the target gene and nowhere else in the genome.

"Then the RNA plus the protein [Cas9] will cut like a pair of scissors the DNA at that site, and ideally nowhere else," Church explained. Once the DNA is cut, the cell's natural repair mechanisms kick in and work to piece the DNA back together, and at this point, edits can be made to the genome. There are two ways this can happen:

According to the Huntington's Outreach Project at Stanford University, one repair method involves gluing the two cuts back together. This method, known as "non-homologous end joining," tends to introduce errors where nucleotides are accidentally inserted or deleted, resulting in mutations that could disrupt a gene.

In the second method, the break is fixed by filling in the gap with a sequence of nucleotides. In order to do so, the cell uses a short strand of DNA as a template. Scientists can supply the DNA template of their choosing, thereby writing-in any gene they want, or correcting a mutation.

Scientists originally discovered the CRISPRs in bacteria in 1987, but they didn't initially understand the biological significance of the DNA sequences, and they didn't yet call them "CRISPRs," according to Quanta Magazine (opens in new tab). Yoshizumi Ishino and colleagues at Osaka University in Japan first found the characteristic nucleotide repeats and spacers in the gut microbe Escherichia coli, and as the technology for genetic analysis improved in the 1990s, other researchers found CRISPRs in many other microbes.

Francisco Mojica, a scientist at the University of Alicante in Spain, was the first to describe the distinct characteristics of CRISPRs and found the sequences in 20 different microbes, according to a 2016 report (opens in new tab) in the journal Cell. At one point, he dubbed the sequences "short regularly spaced repeats" (SRSRs), but he later suggested that they be called CRISPRs instead. The term CRISPR first appeared in a 2002 report, published in the journal Molecular Microbiology and authored by Ruud Jansen of Utrecht University, with whom Mojica had been in correspondence.

In the following years, scientists also discovered Cas genes and the function of Cas enzymes, and they figured out that the spacers in CRISPRs came from invasive viruses, Quanta reported.

Among these pioneering researchers was Jennifer Doudna, a professor of biochemistry, biophysics and structural biology at the University of California, Berkeley, who went on to share the 2020 Nobel Prize in chemistry with Emmanuelle Charpentier, director of the Max Planck Unit for the Science of Pathogens. The two scientists are credited with adapting the bacterial CRISPR/Cas system into a handy gene-editing tool, Live Science previously reported.

Related: Nobel Prize in Chemistry: 1901-Present

Charpentier initially discovered tracrRNA while studying the bacteria Streptococcus pyogenes, which causes a range of diseases from tonsillitis to sepsis. Having uncovered tracrRNA as a previously unknown component of the CRISPR/Cas system, Charpentier began collaborating with Doudna to recreate that system in a test tube. In 2012, the team published their seminal work (opens in new tab) in the journal Science, announcing that they'd successfully simplified the molecular scissors into a gene-editing tool.

Some thought that biochemist Feng Zhang of the Broad Institute might also earn the Nobel for his own, separate work with the CRISPR system, Science Magazine reported. Zhang demonstrated that the CRISPR system works in mammalian cells, and based on this work, the Broad Institute earned the first patent for the use of CRISPR gene-editing technology in eukaryotes, or complex cells with nuclei to hold their DNA.

In 2013, researchers in the labs of Church and Zhang published the first reports describing the use of CRISPR-Cas9 to edit human cells in an experimental setting. Studies conducted in lab dish and animal models of human disease have demonstrated that the technology can effectively correct genetic defects. Examples of such diseases include cystic fibrosis, cataracts and Fanconi anemia, according to a 2016 review article (opens in new tab) published in the journal Nature Biotechnology. These studies have paved the way for therapeutic applications in humans.

In the realm of medicine, CRISPR has been tested in early-stage clinical trials as cancer therapy and as a treatment for an inherited disorder that causes blindness. It's also been investigated as a strategy for preventing the spread of Lyme disease and malaria from viral vectors to people, and it's also been studied in animal models of HIV as a way to rid infected cells of the virus, Live Science previously reported. One research team in China attempted to treat a human patient's HIV using CRISPR, and while the treatment wasn't successful in curing the infection, the gene therapy also didn't cause any harmful effects, Live Science reported.

"I think the public perception of CRISPR is very focused on the idea of using gene editing clinically to cure disease," said Neville Sanjana of the New York Genome Center and an assistant professor of biology, neuroscience and physiology at New York University. "This is no doubt an exciting possibility, but this is only one small piece."

Related: 10 amazing things scientists just did with CRISPR

CRISPR technology has also been applied in the food and agricultural industries to engineer probiotic cultures and to vaccinate industrial cultures (yogurt, for example) against viruses. It is also being used in crops to improve yield, drought tolerance and nutritional properties.

One other potential application is to create gene drives, a genetic engineering technique that increases the chances of a particular trait passing on from parent to offspring; this kind of genetic engineering derives from a natural phenomenon, where specific versions of genes are more likely to be inherited. Eventually, over the course of generations, the trait spreads through entire populations, according to the Wyss Institute. Gene drives could be used for various applications, such as eradicating invasive species or reversing pesticide and herbicide resistance in crops, according to a 2014 report published in the journal Science.

During the COVID-19 pandemic, the CRISPR-Cas9 system has been used to develop various diagnostic tests for the viral infection, BBC News reported.

In addition, CRISPR has recently been used in the following ways:

However, despite its wide range of uses, the tool is not without its drawbacks.

"I think the biggest limitation of CRISPR is it is not a hundred percent efficient," Church told Live Science. That means, in a given experiment, CRISPR may successfully edit only a percentage of the targeted DNA. According to the 2014 Science article by Doudna and Charpentier, in a study conducted in rice, gene editing occurred in nearly 50% of the cells that received the Cas9-RNA complex. Meanwhile, other analyses have shown that depending on the target, editing efficiencies can reach as high as 80% or more.

The technology can also create "off-target effects" when DNA is cut at sites other than the intended target. This can lead to the introduction of unintended mutations. Furthermore, Church noted, even when the system cuts on target, there is a chance of not getting a precise edit. He called this "genome vandalism."

The many potential applications of CRISPR technology raise questions about the ethical merits and consequences of tampering with genomes. And in particular, a slew of ethical debates flared up in 2018 when He Jiankui, formerly a biophysicist at the Southern University of Science and Technology in Shenzhen, announced that his team had edited DNA in human embryos and thus created the world's first gene-edited babies.

He was subsequently sentenced to three years in prison and fined 3 million yuan ($560,000) for practicing medicine without a license, violating Chinese regulations on human-assisted reproductive technology and fabricating ethical review documents, Live Science previously reported. But even after his sentencing, He's experiments raised questions about how the use of CRISPR should be regulated going forward, especially given that the technology is still fairly new.

Related: Here's what we know about CRISPR safety

Illegal experimentation in human embryos represents an extreme misuse of CRISPR, of course, but even seemingly ethical uses of the technology could carry risks, scientists say.

In general, making genetic modifications to human embryos and reproductive cells such as sperm and eggs is known as germline editing. Since changes to these cells can be passed on to subsequent generations, using CRISPR technology to make germline edits has raised a number of ethical concerns.

Variable efficacy, off-target effects and imprecise edits all pose safety risks. In addition, there is much that is still unknown to the scientific community. In a 2015 article published in Science, David Baltimore and a group of scientists, ethicists and legal experts note that germline editing raises the possibility of unintended consequences for future generations "because there are limits to our knowledge of human genetics, gene-environment interactions, and the pathways of disease (including the interplay between one disease and other conditions or diseases in the same patient)."

In the 2014 Science article, Oye and colleagues point to the potential ecological impact of using gene drives. An introduced trait could spread beyond the target population to other organisms through crossbreeding. Gene drives could also reduce the genetic diversity of the target population, potentially hampering its ability to survive.

Other ethical concerns are more nuanced. Should we make changes that could fundamentally affect future generations without having their consent? What if the use of germline editing veers from being a therapeutic tool to an enhancement tool for various human characteristics?

To address these concerns, the National Academies of Sciences, Engineering and Medicine put together a comprehensive report with guidelines and recommendations for genome editing.

Although the National Academies urge caution in pursuing germline editing, they emphasize "caution does not mean prohibition." They recommend that germline editing be done only on genes that lead to serious diseases and only when there are no other reasonable treatment alternatives. Among other criteria, they stress the need to collect data on the health risks and benefits and to maintain continuous oversight during clinical trials. They also recommend that, after a trial concludes, trial organizers should follow up with the participants' families for multiple generations to see what changes persist in the genome over time.

This article includes additional reporting by Alina Bradford, Live Science contributor.

Originally published on Live Science.

Continued here:
What is CRISPR? | Live Science

Against the backdrop of the cost-of-living crisis it is argued that the UK could bolster food security, combat climate change and lower food prices by relaxing the rules on and around genetic engineering. By designing more resistant crops which are less reliant on fertiliser and are more nutritious, progress could be made. On the other hand, this may be a short-sighted approach to deregulation and taking the risk could result in disastrous consequences.

The Genetic Technology (Precision Breeding) Bill 2022

The arguments are surfacing as The Genetic Technology (Precision Breeding) Bill (GT (PB) Bill) which is currently in the House of Commons at the report stage (allowing the House to consider further amendments) heading for its 3rd reading. Much of the debate centres around the understanding of the technology.

Genetically Modified Organisms (GMOs) are organisms in which the genetic material (DNA or RNA) has been altered in a way that does not occur naturally, and the modification can be replicated and/or transferred to other cells or organisms. This typically involves the removal of DNA, manipulation outside the cell and reinsertion into the same or other organism. Gene editing (GE) is arguably different as rather than inserting new DNA it edits the organisms own DNA - which could happen over time, but this essentially speeds up the natural process. Both plants and animals can be genetically manipulated.

Regulation (EC) No 1829/2003 provides the general framework for regulating genetically modified (GM) food in the EU with a centralised procedure for applications to place GM food on the EU market. It focusses on the traceability and labelling of GMO and the traceability of food and feed products to ensure a high level of protection of human life and health. GM foods can only be placed on the market after scientific risk assessment of the risks to human health and the environment.

The EU implemented these regulations back in 2001 which heavily restricted the use of GMOs and it has maintained that conservative position since. To continue not to allow GMOs is at odds with other countries, such as Australia, Japan and the US. As the technology developed several member states (including the UK) felt that a more relaxed approach to genetic editing would be beneficial. However, in 2018 the European Court of Justice in, Confederation Paysanne v Premier Minister (C-528/16) decided that there was no real distinction with gene editing (also described as Precision breeding) and they were to be treated as GMOs within the meaning of the GMO Release Directive 2001.

Nevertheless, in the UK in 2019 the then prime minister famously declared that he would liberate the U.K.s extraordinary bio science sector from anti-genetic modification rules. Consequently, since leaving the EU the UK has been working on moving away from the EUs stricter definition of a GMO as evidenced by the GT (PB) Bill.

The Bill defines precision bred to be, if any, or every feature of its genome results from the application of modern biotechnology and every feature of its genome could have resulted from either traditional processes or natural transformation.[1]

It is argued that this removes unnecessary barriers to innovation inherited from the EU to allow the development and marketing of precision bred plants and animals, which will drive economic growth and position the UK as a leading country in which to invest in agri-food research and innovation.

The main elements of the Genetic Technology (Precision Breeding) Bill are:

Creating a new, simpler regulatory regime for precision bred plants and animals that have genetic changes that could have arisen through traditional breeding or natural processes. No changes are proposed to the regulation of animals until animal welfare is safeguarded.

Introducing two notification systems for research and marketing purposes where breeders and researchers will need to notify Department for Environment, food and Rural Affairs (Defra) of precision bred organisms. The information collected on precision bred organisms will be published on a public register.

Establishing a new science-based authorisation process for food and feed products developed using precision bred organisms.

This is the result of an All-Party Parliamentary Group which called for amendments to be made in 2020 to the, at the time, forthcoming Agriculture Bill 2019-21 (now the Agriculture Act 2020) to allow precision breeding in the UK.

The amendments would require changes to the UK Environmental Protection Act 1990, including changing the use of the EU definition of a GMO which would allow UK scientists, farmers and both plant and animal breeders access to gene editing technologies that other countries outside the EU have.

The focus in the UK is to allow traditional breeding methods to alleviate some of the effects such as extreme weather, food shortages, the cost-of-living crisis and to encourage pest-resistance.

The Genetically Modified Organisms (Deliberate Release) (Amendment) (England) Regulations 2022

On 11th April 2022, the Genetically Modified Organisms (Deliberate Release) (Amendment) (England) Regulations 2022 implemented an alignment of GE with the regulation of plants using traditional breeding methods. The Regulations removed the need to submit a risk assessment and seek consent from the Secretary of State before releasing certain GE plants for non-marketing purposes. They apply to England only.

This will allow for the release and marketing of gene edited products under certain circumstances that has so far been prohibited by the EU. It will allow UK scientists to develop plant varieties and animals with beneficial traits that could also occur through traditional breeding and natural processes, while providing safeguards in both marketing and authorisations via regulation.

Taking a Risk?

Another consequence of leaving the EU is that the Food Standards authority (FSA) is now responsible for authorising Novel foods applications in the UK. The FSA points to this need for authorisation as a further check and balance on any risks that may arise from a divergence from EU regulation.

Although it is argued that the Bill may have been drafted a little hastily, any food developed using new technology is subject to the scientific scrutiny of a Novel foods application. If there is a risk of unintended consequences from GE (it is argued that there is a risk of unidentified and untested mutations resulting from gene editing) the role of regulatory authorities such as DEFRA and the FSA is to ensure that no unintended product gains approval.

The debate is becoming increasingly focussed as the cost-of-living crises deepens.

Co-Authored by Laura Hipwell, Trainee Solicitor at CMS.

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To modify or not to modify? Genetic Modification and Gene Editing - A divergence by the UK - Lexology

THE double helix structure of DNA was discovered in 1953, but at the time the structure of genes themselves remained unknown. But the term gene had already been in use for decades as a convenient term for the mysterious basic unit of heredity.

Writing in 1911, the Danish botanist Wilhelm Johannsen referred to the term as nothing but a very applicable little word, easily combined with others. Once it was understood that genes were made of DNA, new questions opened up.

In the 1950s and onwards, the only organisms that could really be investigated in detail were microorganisms. As a result, almost all early molecular biology was done on bacteria and their viruses.

A bacterial chromosome contains many genes. Escherichia coli, the most-studied bacterial species, has a circular chromosome that has thousands of genes, arranged one after the other.

Could it be possible to make a molecule of DNA that consisted of only one of these genes in other words, to isolate a gene from the chromosome?

One of the most-studied groups of genes in this early period was the lac operon. An operon is a small set of neighbouring genes under the influence of a single molecular switch.

The lac operon contains genes that encode proteins that allow for lactose to be used as an energy source, allowing the production of these proteins to be turned on only when another sugar is not present. French scientists Francois Jacob and Jacques Monod won a Nobel Prize in 1965 for uncovering how this system of genetic regulation worked.

In 1969, scientists at Harvard managed to make a DNA molecule that contained only the lac operon and no other genes. To do this, they used two viruses of bacteria which, together with other genes, carried the lac operon in opposite orientations.

These could then be joined together to create a double helix molecule with only the lac operon on it. This meant they had isolated a small set of genes which could be entirely switched on or off with a single molecular switch, which allowed amazing possibilities for future experiments.

The team felt the findings were so important that they held a press conference to announce them. But unusually, this was not framed as a positive announcement: Jon Beckwith, the leader of the research, described the possible implications of their own work as frightening.

In a New York Times article on this brilliant isolation of a gene, appearing underneath a piece on dialogue between East and West Germany, scientist Jim Shapiro was quoted as saying that the work may have bad consequences over which we have no control possibilities such as genetic warfare.

A graduate student involved wrote afterwards that the only reason the news was released to the press was to emphasise its [the sciences] negative aspects. The atmosphere Beckwith promoted in his group was unusual and came from his political convictions.

In the same year that the lac operon paper was published, he accepted the Eli Lilly award, a prominent award for microbiologists funded by a pharmaceutical company.

In his acceptance speech, he stated science in the hands of the people who rule this country and who run our industries is being used to exploit and oppress people all over the world.

He then donated all of the prize money to the Black Panther movement: one half of the prize money to the Boston Panther Free Health Movement and the other half to the Defence Fund for the Panther 21 in New York.

Beckwith knew that, unlike genes, science could never be isolated from its social and political context. The field that developed out of these discoveries already had a name by 1969: genetic engineering.

These days genetic engineering has become a huge field that involves applications, not just experiments in the lab. However, many of the crucial tools continue to be developed from microorganisms.

Viruses and bacteria deal with genes entering and leaving their genomes all the time. As a result, their evolution has produced many exquisite solutions for gene manipulation: recombinant DNA and CRISPR being two famous examples.

Gene therapy based on these tricks to deliver new genetic material into the human genome is already being used in clinical medicine.

With growing databases of known genomes, scientists can now search systematically for evolutionary solutions that might be adapted further for human genetic engineering.

In a Nature Biotechnology paper out this week, scientists from Stanford and Berkeley computationally searched through nearly 200,000 genomes to predict new enzymes belonging to a type known as large serine recombinases.

These enzymes can recombineDNA, meaning they integrate new DNA into specific sites in a genome an ideal tool for genetic engineering.

They then experimentally tested these recombinases and their integration sites, they managed to increase the number of known enzymes and corresponding sites by over 100 times.

The scientists write in an understated way that their work has potential clinical and research utility. The new catalogue of recombinases does offer huge potential for gene therapy, replacing missing or mutated genes in very sick patients.

But genetic engineering also has risks. As the New York Times noted in 1969, it is nice to believe that the powers of science will be used only for benefit but every days newspaper provides evidence suggesting that the contrary may be true. The political convictions of the lead scientist in 1969 made a huge difference to the understanding of the research in public.

The lead scientist, Patrick Hsu, is a founder of the Arc Institute, a non-profit but independent research organisation co-founded with scientist Silvana Konermann and the entrepreneur Patrick Collison, the CEO of payments company Stripe.

The aim of Arc is a new model of science funding to get important discoveries into the public domain as quickly as possible. The announcements from the Arc Institute are relentlessly positive.

But the nuanced message of Beckwiths press conference during the beginnings of the field should stay with us as a warning: what happens after a scientific discovery is important. Responsible science means articulating risks as well as benefits.

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DNA and the impossibility of research in isolation - Morning Star Online

The Steering Committee for Human Rights in the fields of Biomedicine and Health (CDBIO)* has achieved the final step of the re-examination process of Article 13 of the Convention on Human Rights and Biomedicine (Oviedo Convention) with the adoption of the clarifications on the scope of the provisions with regard to research and the purposes limitation provided for any intervention on the human genome.

In June 2021, as a first conclusion, the Committee had agreed that taking into account the technical and scientific aspects of theses developments, as well as the ethical issues they raise, it considered that the conditions were not met for a modification of the provisions of Article 13. However, it agreed on the need to provide clarifications, in particular on the terms preventive, diagnostic and therapeutic and to avoid misinterpretation of the applicability of this provision to research.

These clarifications were adopted by the CDBIO at its 1st plenary meeting (31 May 3 June 2022) and presented to the Committee of Ministers on 27 September 2022.

In this video, Anne Forus, Chair, and Pete Mills, member, of the CDBIO Drafting group on genome editing present the context, the content and the importance of these clarifications.

Context

This re-examination process of Article 13 was undertaken within the framework of the Strategic Action Plan on Human Rights and Technologies (2020 2025), as part of the actions planned under its Governance pilar and the specific objective of embedding human rights in the development of technologies which have an application in the field of biomedicine.

As underlined by the DH-BIO in November 2018, ethics and human rights must guide any use of genome editing technologies in human beings in accordance with the Convention on Human Rights and Biomedicine (the Oviedo Convention, 1997) - the only international legally binding instrument addressing human rights in the biomedical field which provides a unique reference framework to that end. The Oviedo Convention represents the outcome of an in-depth discussion at European level, on developments in the biomedical field, including in the field of genetics.

Article 13 of the Convention addresses these concerns about genetic enhancement or germline genetic engineering by limiting the purposes of any intervention on the human genome, including in the field of research, to prevention, diagnosis or therapy. Furthermore, it prohibits any intervention with the aim of introducing a modification in the genome of any descendants. This Article was guided by the acknowledgement of the positive perspectives of genetic modification with the development of knowledge of the human genome; but also by the greater possibility to intervene on and control genetic characteristics of human beings, raising concern about possible misuse and abuses.

More information:

* In January 2022, the CDBIO took over the responsibility of the Committee on Bioethics (DH-BIO) as the committee responsible for the conduct of the intergovernmental work on human rights in the fields of biomedicine and health. The CDBIO is also advising and providing expertise to the Committee of Ministers of the Council of Europe on all questions within its field of competence.

Read more from the original source:
Genome editing technologies: final conclusions of the re-examination of Article 13 of the Oviedo Convention - Council of Europe

San Diego, CAThe annual Cell & Gene Meeting on the Mesa in San Diego kicked off this week with a packed schedule of sessions and some 40 company presentations that speak to the significant progress in these burgeoning therapeutic fields.

Organized by the Alliance for Regenerative Medicine, the program has attracted more than 1,700 attendees, 20% of whom are C-level executives. Although opting for a hybrid format, the enthusiastic number of live attendees signaled the thrill and benefits of live conferences and networking.

Commercialization is around the bend

The opening plenary session covered current trends and challenges surrounding gene therapy commercialization. Moderated by Dave Lennon, PhD, CEO of Satellite Bio, the panel discussed critical topics related to bringing these potentially life-changing treatments to market: pricing, the hurdles of early access, accelerated approval requirements, novel go-to-market challenges, and considerations of global equity.

Arguably the key rate-limiting step for commercialization is regulatory approval. Debbie Drane, senior vice president (SVP) of Global Commercial Development and Therapeutic Area (TA) Strategy at CSL Behring, discussed how regulators do not understand all diseases equally. Some of the targeted rare diseases do not have a clinical or regulatory precedent. Regardless of a regulatory bodys familiarity with a disease, Drane thinks making durability claims with gene editing can be tricky. For example, CSL Behrings EtranaDez, potentially the first gene therapy for patients living with hemophilia B, accepted by the FDA for priority review last May, will have to be compared to existing chronic treatments.

Regarding access to gene therapy before approval, Matthew Klein, MD, chief operating officer (COO) at PTC Therapeutics, said, Were in a special situation with one-time administered gene therapies. Thats different than when you have a repeat-administered small molecule, for example, where you can leverage compassionate use programs and expanded access programs to accelerate commercialization on the other side of approval. Obviously, with a one-time administrative therapy, you must think carefully about how that plays out.

Klein laid out PTCs different approaches, including early access programs to leverage treating patients before finalizing pricing and negotiation. Were looking to European countries like France with early access programs that allow us to provide commercial drugs prior to finalizing reimbursement discussions, he said.

Upon drug approval, one of the first things that happen is that patients and families worldwide start to reach out. According to Leslie Meltzer, PhD, chief medical officer (CMO) at Orchard Therapeutics, this is a relationship that needs to be cultivated from the earliest stages of development.

Meltzer said companies need to consider what questions the patient communities might have about the safety and efficacy of therapy and how to motivate participation in a corresponding clinical trial. Meltzer advocates for early and frequent patient engagement with a unified voice on the value of a gene therapy product. This can be transformative in reaching communities and setting expectations about timelines and whats involved with therapy.

The high price of one-shot cures

On pricing, Thomas Klima, Chief Commercial and Operating Officer of bluebird bio, discussed the pricing of the cell-based gene therapy product Zynteglo, approved by the FDA in August to treat beta-thalassemia, which will cost $2.8 million per patient. Klima highlighted that people with the most severe form of beta-thalassemia live their lives tethered to the healthcare system. They require regular transfusions and spend an average of 9.8 hours every three to four weeks in a hospital to receive the blood transfusions necessary for survival. Klima claimed that lifetime treatment for transfusion-dependent thalassemia costs more than $6 millionwhich is in line with the projection of $5.4 million from a recent study by Vertexand argued for the value of bluebirds treatment for $2.8 million.

For how commercialization models can expand and evolve, Christine Fox, president of Novartis Gene Therapies, said that part of the equation is bringing these treatments to countries around the world. At the heart of this problem is bringing patient advocacy and medical advisory to countries greatly affected by the clinical indication.

Overall, there was optimism that there would be an upswing in approved gene therapy products, as evidenced by a growing number of clinical trials using CRISPR gene editing. The first-ever approval of a CRISPR gene-editing therapy could be less than a year away. At the same time, base editing has already entered the clinic, and the first in vivo CRISPR approaches are progressing in clinical trials. This progress reflects how much has been learned in assembling the necessary pieces to get these treatments to commercialization, from development and manufacturing to the clinical and regulatory side of the equation.

More than one way to skin a [gene editing] cat

Another interesting session at the Cell & Gene Meeting on the Mesa offered forecasts of near- and longer-term future breakthroughs in clinical genome editing, featuring the CEOs of LogicBio, Homology Medicines, and Arbor Biotechnology as well as the CSO of Editas Medicine.

Devyn Smith, PhD, CEO at Arbor Biotechnologies, said investors understood the promise of genome editing, noting that the valuations of key public companies have held up remarkably well considering the market turmoil over the past two years. [It] is incumbent on all of us in this space to continue executing and hopefully generating positive clinical data so that momentum continues, Smith said.

Mark Shearman, PhD, CSO at Editas Medicine, agreed. With any new technology, the [focus is] on clinical data and proving that its safe and efficacious. Typically, [investors] also want to see a projection of where the programs going and a timeline over which youll be able to submit an application. Theyre also interested in whether you are in control of the technology and have all the infrastructures to monitor the technology to be confident that you can advance it. Lastly, if you have examples where a regulatory authority has reviewed your process and analytics, confidence boosts when approved or accepted.

Tim Farries, PhD, Principal Consultant and Senior Director with the consultancy Biopharma Excellence, also questioned the benefit of launching gene editing programs on rare diseases with small populations to show the relative ease and benefits before expanding to broader indications and populations. But for the most part, genome editing involves modifying DNA at one specific site. Thats why you see gene editing therapies in monogenic disorders right nowbecause you have to know exactly what part of the genome is contributing at a big effect size to the disease that youre trying to treat, said Albert Seymour, PhD, President and CEO at Homology Medicines. Thats a great place to start as we understand a little bit more about larger monogenic indications.

During a discussion on choosing between developing editing tools or understanding biological targets, all panelists hedged towards editing technology. Fred Chereau, president and CEO of LogicBio, favored starting with the editing technology because its where the safety concerns can emerge. Understanding an editing technologys efficiency and precision helps inform product development.

That said, each disease will require a different approach. According to Smith, certain indications will require a cut-and-kill approach to knock out or down a gene, changing an individual base or a series of bases, or impacting regulatory regions. The reality is there are going to be a lot of different ways weve got to skin this cat, and its not going to be one-size-fits-all, said Smith.

Another question addressed what payers would like to see gene editing show over the next three to five years. Shearman answered, For the rare disease area, this should get worked out pretty quickly because, ultimately, [it] wont be an issue of money based on the number of patients. I think the transition to treating large patient populations is going be an interesting one.

Smith said that someone could be wildly successful and completely upend the payers way of doing things. Its an opportunity for new upstarts to come in and figure out new different approaches to innovate, he said. On trying to fit the current approach to reimbursement into the one-and-done therapies, Smith added, its not even a square peg-round holetheyre in different planets. Something has got to give somewhere. This will require different thinking because applying existing models will limit access to patients.

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Approval, Commercialization Highlighted at Cell & Gene Meeting on the Mesa - Genetic Engineering & Biotechnology News

Photo: Galpagos finch, by Mike's Birds from Riverside, CA, US, CC BY-SA 2.0 , via Wikimedia Commons.

Editors note:We are a delighted to present a new series by biologist Jonathan Wells asking, Is Darwinism a Theory in Crisis? This is the third post in the series, which is adapted from the recent book,The Comprehensive Guide to Science and Faith.Find the full series here.

A scientific revolution is fueled in part by growing dissatisfaction among adherents of the old paradigm. This leads to new versions of the theoretical underpinnings of the paradigm. In his 1962 bookThe Structure of Scientific Revolutions, philosopher of science Thomas Kuhn wrote:

The proliferation of competing articulations, the willingness to try anything, the expression of explicit discontent, the recourse to philosophy and to debate over fundamentals, all these are symptoms of a transition from normal to extraordinary research.1

A growing number of biologists now acknowledge that there are serious problems with modern evolutionary theory. In 2007, biologist and philosopherMassimoPigliucci published a paper asking whether we need an extended evolutionary synthesis that goes beyond neo-Darwinism.2The following year, Pigliucci and 15 other biologists (none of them intelligent design advocates) gathered at the Konrad Lorenz Institute for Evolution and Cognition Research just north of Vienna to discuss the question. Science journalist Suzan Mazur called this group the Altenberg 16.3In 2010, the group published a collection of their essays. The authors challenged the Darwinian idea that organisms could evolve solely by the gradual accumulation of small variations preserved by natural selection, and the neo-Darwinian idea that DNA is the sole agent of variation and unit of inheritance.4

In 2011, biologist James Shapiro (who was not one of Altenberg 16 and is not an intelligent design advocate) published a book titledEvolution: A View from the 21st Century. Shapiro expounded on a concept he callednatural genetic engineeringand provided evidence that cells can reorganize their genomes in purposeful ways. According to Shapiro, many scientists reacted to the phrase natural genetic engineering in the same way they react to intelligent design because it seems to violate the principles of naturalism that exclude any role for a guiding intelligence outside of nature. But Shapiro argued that

the concept of cell-guided natural genetic engineering is well within the boundaries of twenty-first century biological science. Despite widespread philosophical prejudices, cells are now reasonably seen to operate teleologically: Their goals are survival, growth, and reproduction.5

In 2015,Naturepublished an exchange of views between scientists who believed that evolutionary theory needs a rethink and scientists who believed it is fine as it is. Those who believed that the theory needs rethinking suggested that those defending it might be haunted by the specter of intelligent design and thus want to show a united front to those hostile to science. Nevertheless, the former concluded that recent findings in several fields require a conceptual change in evolutionary biology.6These same scientists also published an article inProceedings of the Royal Society of London,in which they proposed an alternative conceptual framework, an extended evolutionary synthesis that retains the fundamentals of evolutionary theory but differs in its emphasis on the role of constructive processes in development and evolution.7

In 2016, an international group of biologists organized a public meeting to discuss an extended evolutionary synthesis at the Royal Society in London. Biologist Gerd Mller opened the meeting by pointing out that current evolutionary theory fails to explain (among other things) the origin of new anatomical structures (that is, macroevolution). Most of the other speakers agreed that the current theory is inadequate, though two speakers defended it. None of the speakers considered intelligent design an option. One speaker even caricatured intelligent design as God did it, and at one point another participant blurted out, NotGod were excluding God.8

The advocates of an extended evolutionary synthesis proposed various mechanisms that they argued were ignored or downplayed in current theory, but none of the proposed mechanisms moved beyond microevolution (minor changes within existing species). By the end of the meeting, it was clear that none of the speakers had met the challenge posed by Mller on the first day.9

A 2018 article inEvolutionary Biologyreviewed some of the still-competing articulations of evolutionary theory. The article concluded by wondering whether the continuing conceptual rifts and explanatory tensions will be overcome.10As long as they continue, however, they suggest that a scientific revolution is in progress.

Next,Theory in Crisis? Circling the Wagons.

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Dissatisfaction and New Articulations - Discovery Institute