Tag: CRISPR

New study uses the gene editing tool CRISPR to finally discover how the wings of insects evolved.

After intelligence probably the most astounding ability created by evolution during the history of life is the miracle of flight. The ability to fly gives such an advantage to any living creature that wings have evolved at least four separate times in different animal groups. These groups include the insects, the birds, the mammals and even the reptiles.

Flight has evolved in many very different kinds of animals. (Credit: Pinterest)

The insects were the first to take to the air and fly. We have fossil evidence of flying insects from as far back as the Devonian period when our vertebrate ancestors were just climbing out of the water. Evolutionary biologists have for many years theorized that the first insect ‘proto-wing’ developed not as a organ of flight but instead as an organ to help an insect regulate its body temperature.

The largest insect of all time was named Meganeuridae who lived during the Pennsylvania Period and had a 60-70 cm wingspan. (Credit: Geology In)

You see insects are cold-blooded and on a chilly morning many use the light of the Sun to try to warm up their metabolism. A knob on the insect’s back would increase the amount of the Sun’s heat that the insect could absorb, just like a solar panel, and the bigger the knob the better. Natural selection would then act so as to increase the size of the knobs until they became ‘proto-wings’ that an insect could at first use to glide or even catch the wind for a free ride. As the new wings grew even larger, and acquired muscles that allowed them to move, eventually the insect was able to fly.

Before they evolved for flight Insect wings were used as solar collectors to help the insect warm up their metabolism. (Credit: Ohio’s Electric Cooperatives)

Some modern insects still use their wings in that way. If you’ve ever taken a walk in a swampy area early in the morning you can find dragonflies and damselflies climbing up the stalks of tall grasses or reed. Climbing not flying because their metabolism hasn’t warmed up enough to produce the energy needed to fly. Once near the top the dragonfly will spread it’s wings to face the Sun in order to absorb the warmth of the sunlight which will increase its body temperature so that it can fly.

 So the question for biologists to answer was, where did those original knobs come from? For over a century entomologists looked in vain among the closest relatives of insects the myriapods, that is the centipedes and millipedes for some structure that could have evolved into those knobs. The search was in vain however because, as modern DNA analysis has shown, insects are actually more closely related to crustaceans, shrimp, lobsters and crabs than they are to centipedes and millipedes.

For many years biologists thought that insects were most closely related to centipedes and millipedes. Here’s a quick way to tell the difference between them! (Credit: Seed to Feed Me)
Modern DNA analysis has shown that insects are actually more closely related to shrimp and other crustaceans. (Credit: Arizona Aquatic Gardens)

And now a new study from biologists at the Marine Biological Labouratory (MBL) at Woods Hole has discovered the original bump on a shrimp’s leg that developed into the wings of insects. In a paper published in the journal Nature Ecology & Evolution, Research Associate Heather Bruce along with MBL director Nipam Patel have used the gene editing tool CRISPR to demonstrate how a lobe on the seventh, innermost segment of a crustacean’s leg was incorporated into the body of the ancestors of early insects as they moved onto the land. This segment provided extra strength to the exoskeleton of the early insects. In time the lobe then grew to become the long sought after ‘proto-wing’.

The gene editing tool CRISPR is revolutionizing many different fields of biological research. (Credit: Vox)

Doctor Bruce began by comparing the genetic instructions for the segmented legs of a tiny beach hopper shrimp called Parhyale to those in the fruit fly Drosophila and the beetle Tribolium. Now Parhyale, like all crustaceans have seven segments in their legs while both Drosophila and Tribolium, like all insects have only six segments. However all three species have an identical sequence of five genes that code the instructions for leg development.

Morphology of the legs of an ancestral crustacean, a modern shrimp (Parhyale) and an insect. (Credit: Nature Ecology and Evolution, Bruce & Patel)
Comparing the legs of Parhyale and an insect it is now clear that the Coxal plate of the shrimp is the structure that evolved into the insect wing. (Credit: Nature Ecology and Evolution, Bruce & Patel)

Using CRISPR Bruce disabled those five genes in embryos of all three species one at a time and monitored the results. What she found was that eliminating the genes eliminated the six leg segments farthest from the body. She also found that the seventh, nearest segment of the leg of Parhyale corresponds to a section of the back of the exoskeleton of the insects. Most importantly, a lobe on that seventh segment, called the Tergal Plate moved with the segment becoming a perfect candidate for the knob that evolved into the insect wing. The story of the evolution of the insect’s wing clearly demonstrates the power of natural selection in taking a structure in the body of an animal and altering its shape to perform an entirely new function. The story of how DNA analysis and gene editing have enabled scientists to work out the details of that evolution clearly show the power of the newest tools that biologists possess in their study of life here on Earth.

The Nobel Prizes for Science in 2020 are Announced.

Early October is always that time of year when we all take a moment from the mundane news to recognize those scientists who are making fundamental contributions to our knowledge of the world around us. The cause of this annual ceremony is of course the announcement of the winners of the Nobel Prizes for the natural sciences of Physics, Chemistry, and Physiology.

The Nobel Prize. Oh, there’s also about a million bucks involved as well. (Credit: Phys.org)

This year the Physiology, i.e. Medicine prize was announced first and has been awarded jointly to Harvey J. Alter, Charles M. Rice, both of the United States, along with British Born Michael Houghton. Fittingly in this year of the Covid-19 pandemic the work for which these three scientists have been recognized deals with the identification of and drug treatments for the deadly viral disease, Hepatitis C.

This Year’s prize winners for Medicine are (left to right) Harvey J. Alter, Michael Houghton and Charles M. Rice. (Credit: Firstpost)

Hepatitis in general is classified as an inflammation of the liver and is most commonly caused by one of five different viruses giving rise to Hepatitis A, B, C, D and E. Of these Hepatitis A and B were the first to be studied and vaccines are now available to provide immunity against those forms of the disease. The cause of Hepatitis C however remained elusive for many years, making the search for effective means of treatment difficult.

Hepatitis is really several diseases that all cause an inflammation of the liver. Hepatitis is a very serious disease that if left untreated often results in death. (Credit: DW)

It was in the 1960s that Doctor Alter succeeded in demonstrating that Hepatitis C was in fact a completely different disease from the types known at that time, A and B. Due to Alter’s work Hepatitis C was for a time actually known as Hepatitis ‘non-A’, ‘non-B’.

Following up on Alter’s work Doctor Houghton then was able to isolate the genetic structure of a previously unknown virus in Hepatitis patients. Finally it was Doctor Rice who showed that the new virus alone could cause Hepatitis. Once the cause of Hepatitis C was known tests and treatment techniques could be developed for the virus so that today Hepatitis C is a treatable disease.

Like all viruses the Hep C virus is simply a strand of genetic material, RNA in this case, surrounded by a protective shell of proteins and lipids. (Credit: Wikipedia)

The Physics prize came second and was also awarded to a trio of scientists. Sir Roger Penrose of Oxford University in the UK received half of the award while Reinhard Genzel of Germany and Andrea Ghez of the United States shared the other half. The three were all honoured for their pioneering work on Black Holes.

The 2020 Nobel Physics recipients are (left to right) Sir Roger Penrose, Reinhard Genzel and Andrea Ghez. (Credit: Hindustan Times)

In fact it was Sir Roger, along with the late Stephen Hawking who were the first physicists to take seriously the idea that the odd solutions to Einstein’s field equations might have a physical reality. (Einstein himself could never made up his mind on whether or not black holes existed.) Penrose and Hawking spent decades mathematically working out the details of what a black hole would look like (pun intended). For much of that time they continued working despite the fact that there was absolutely no observational evidence to confirm any of their theories.

Perhaps the two men most associated with Black Holes. Stephen Hawking (l) and of course Albert Einstein. (Credit: ABC)

In fact much of the first evidence for black holes came from the work of Genzel and Ghez who were investigating the supermassive object at the center of our galaxy known as Sagittarius A. Using some of the world’s largest telescopes Genzel and Ghez developed techniques to see through the clouds of gas in the Milky Way’s center. Those techniques enabled them to study Sagittarius A and demonstrate that it was an immense black hole, confirming many of the theories of Penrose and Hawking. Supermassive black holes like Sagittarius A are now thought to exist at the center of every large galaxy.

In the constellation of Sagittarius lies the center of our Milky Way galaxy. There sits a supermassive black hole millions of times as massive as our Sun. (Credit: NASA)

So if Sir Roger is now getting a Nobel Prize why isn’t Hawking? The answer to that question is easy, he’s dead and according to the terms of Alfred Nobel’s will that set up the Nobel prizes only living persons can receive the award. If you think that’s not fair, well it really isn’t. However, this is actually not the first time that a scientist has died before his work was sufficiently confirmed to be considered for the prize.

Actually I rather doubt that any of this year’s physics recipients would have won their awards if it hadn’t been for last year’s ‘photograph’ of a black hole, see my post of 17 April 2019. That image was the confirmation of many theories about black holes and undoubtedly convinced the Nobel committee that it was time for researchers studying black holes to finally be recognized.

The first ‘photo’ of a Black Hole, actually taken at microwave frequencies. This is the supermassive black hole in M87 and the accretion disk around it. (Credit: NPR)

No such prompting was required in order to choose the recipients of this year’s chemistry prize. Emmanuelle Charpentier of the Max Planck Institute in Berlin and Jennifer A. Doudna were honoured for their work on the gene editing tool CRISPR. See my posts of 5 August 2017, 1 December 2018 and 18 Aug 2019 for discussions of just how enormous a breakthrough CRISPR is.

CRISPR is the most accurate and precise tool yet discovered for the editing of genetic material. (Credit: YouTube)

The award to Doctors Charpentier and Doudna is unusual for several reasons. One reason is that the first major papers describing CRISPR were published less than a decade ago in 2011 and 2012. Nobel prizes are normally awarded for work that dates back several decades, remember what I said about Roger Penrose and Stephan Hawking above. This is in order to make certain that a great deal of conformational evidence has been accumulated supporting the work before the prize is awarded.

Over the last half dozen years however CRISPR has proven to be such a marvelous tool for genetic studies that the evidence of its importance is overwhelming. CRISPR has given science the most precise and useful tool that it has ever had for literally changing the code of life itself and we are only at the beginning of understanding all that it can do.

The other reason that this year’s chemistry prize is notable is because it represents the very first time that two women have shared the prize. It is unfortunately true that the majority of Nobel Prize winners are white men, with a small number of Asian men thrown in.

Like Hypatia of Alexandria Women have often made important contributions to science and mathematics. (Credit: Historic Mysteries)

Personally I want both greater female and minority participation in the sciences because the more scientists we have, whatever their colour or sex, the more discoveries we will get. For that reason I congratulate Doctors Charpentier and Doudna and hope that other women will soon join them in making equally important advances in our understanding of the Universe. Like Doctors Alter, Rice, Houghton, Penrose, Genzel and Ghez, and hey, let’s not forget Hawking, they all deserve our recognition for their work of discovery. 

In a revolutionary experiment scientists are using the Gene editing tool CRISPR to treat patients suffering with the genetic disorder Sickle Cell Anemia.

In all of modern science there is perhaps no more rapidly advancing field than that of genetic research. Much of that progress has come about because of the development of the molecular gene editing tool CRISPR (which stands for Clustered Regularly Interspaced Short Palindromic Repeats) that allows biochemists to literally cut and/or paste sections of DNA into the chromosomes of living cells. I have talked about CRISPR several times in previous articles, see posts of 2 March 2019, 12 January 2019, 1 December 2018, 1 September 2018 and 5 August 2017, and the full potential of CRISPR is still only being guessed at.

How CRISPR Works (Credit: Cambridge University Press)

Now the latest experiment is making a bold and daring attempt to treat fully grown persons who are sufferers of the inherited genetic disorder Sickle Cell Anemia, a condition that affects about 100,000 people living here in the United States and millions of others worldwide. This is the first ever attempt to use CRISPR to modify the cells of adult patients in the hopes that the altered cells will allow those patients to live a more normal life.

The Genetic disease Sickle Cell Anemia is a chronic ailment for millions of people (Credit: Familydoctor.org

Before I continue let me talk a little bit about the genetic disease Sickle Cell Anemia. This is a disorder that affects the bone marrow and leads to the production of red blood cells with a defective protein that causes the cells to be deformed, sickle shaped. These deformed blood cells are thereby unable to carry a normal amount of oxygen leading to a permanent and in some cases crippling weakness in the affected person. Most sufferers of Sickle Cell Anemia are ethnic African or African-American and since the disease is inherited it can devastate a family for generations.

Sickle Cell Anemia is an inherited genetic disorder (Credit: Synthego)

The procedure being tested is to take cells from the patient’s bone marrow and modify the cells DNA using CISPR in order to make them produce a protein that is normally only formed by the human body while in the womb and during early childhood. It is hoped that the production of this protein will correct the deformations of blood cells caused by the defective protein, thereby alleviating the anemia caused by sickle cell.

Possible Techniques for using CRISPR to cure Sickle Cell (Credit: American Chemical Society)

The experimental treatment for Sickle Cell Anemia is being conducted at eight hospitals and clinics in North America and Europe and is being overseen by CRISPR Therapeutics of Cambridge Massachusetts in association with Vertex Pharmaceuticals of Boston. The current plan is to have up to 45 patients take part in the initial trials of the experiment.

Patient undergoing CRISPR treatment for Sickle Cell Anemia (Credit: NPR)

It will be months before the researchers know for certain whether or not the modified cells are even producing the desired protein let alone if the protein is actually helping to improve the health of the study’s patients. Then, even if there is strong evidence that the procedure has worked, there is the question of how long will the benefits last? Will this technique produce a permanent cure or will the effect be only temporary?

These are questions that only time can answer, but we are at the threshold of a new medical technology. This may be the first attempt to treat patients with a genetic disease by using CRISPR but it certainly will not be the last.

Can Genetically Modified Organisms (GMOs) be used to fight infectious Diseases?

All of the infectious diseases that afflict us have one problem in common that they must solve, how to pass from an infected individual to an uninfected one. Some take the shortest path and move from person to person by touch. Our skin is actually pretty tough however so without a cut or other wound allowing the germs to get inside infection rarely takes place. Some microbes get themselves sprayed into the air by a cough or sneeze in order to be breathed in by their victim, but that’s very much hit or miss with most of the germs left hanging out in space.

A Sneeze can release millions of disease germs ready to infect a healthy person. (Credit: India Today)

Then there are some that actually use another living creature to literally take them from a sick person to new victims. A couple of well known examples of this type of disease are malaria, which uses the mosquito Anopheles gambiae to transmit the bacteria and bubonic plague which uses fleas that are themselves transported by rats. These organisms that pass on diseases from one person to another are referred to a ‘vector’ by epidemiologists and controlling the spread of the vectors, the rats and mosquitoes has often proved to be the most effective way to fight the diseases they spread.

The Anopheles Mosquito carries Malaria one one person to another. (Credit: ZME Science)

Now some biologists are actually trying to use the technology of gene editing to modify the DNA of the vector organisms in an effort to make those species unable to spread the diseases! See my posts of 5Aug17, 1Sept18, 1Dec18 and 12Jan19 for information on gene editing. Two such projects are now reaching the stage where field-testing could soon begin!

 

I mentioned the disease malaria above, a disease that most epidemiologists believe is responsible for the death of half of all the human beings who have ever lived. Think of that, half of all the people who have ever died were killed by the single disease malaria. Even today malaria is a terrible scourge in many parts of the world killing an estimated million people yearly while 300-400 million suffer from the disease.

It’s easy to understand therefore that many efforts are underway to fight this deadly disease. One of these efforts involves the use of gene editing techniques to control the population of the Anopheles gambiae mosquito that transports the malaria germ.

Using the gene-editing tool CRISPR a high security lab in Terni Italy has produced a modified form of female mosquito whose mouth parts resemble those of the males. You see it’s only the female mosquitoes who actually bite, sucking the blood of warm blooded animals in which they incubate their eggs. Females with male mouth parts would be unable to bite, unable to breed in the wild.

GMO Mosquito feeding off of Cow’s Blood (Credit: Pierre Kattar, NPR)

The idea is to artificially breed large numbers of male mosquitoes with the modified gene and release them into the wild. There they will breed and all of their female offspring will be sterile while the male offspring will continue to propagate the edited gene. It is hoped that this will cause the local population to crash, reducing the occurrence of malaria.

The problem, as it always is with gene editing, is unintended consequences. Both genetics and ecology are extremely complex matters that we still know very little about and releasing GMO mosquitoes into the wild will almost certainly alter the environment in unexpected ways. If nothing less, the crash of the Anopheles gambiae population in an area could lead to another species of mosquito, possibly carrying a different disease such as yellow fever to move in to the empty ecological niche.

GMO Mosquitoes are kept tightly controlled at High Security Lab in Terni (Credit: Pierre Kattar, NPR)

The scientists at Terni, led by lab director Ruth Mueller, are aware of the possible dangers, that’s why they’re doing the experiments in a high security lab in order to make certain none of the GMO mosquitoes escape prematurely. To further reduce the danger the mosquitoes will be subjected to long term studies prior to any actual release.

That means that there’s a long way to go and a lot of work still to go on this project but any advance that helps in the fight against malaria would represent a tremendous victory.

 

The second project I’ll discuss involves combating Lyme disease by modifying the DNA of mice. You see the spread of Lyme disease involves a complex back and forth between mice, fleas and deer; it’s really a disease of deer more than it is of humans. Both the mice and fleas are born uninfected but once a mouse is bitten by an infected flea it becomes a carrier and any fleas that subsequently bite the mouse also becomes carriers, and can then pass the disease to a deer, or a human.

Deer Tick infecting someone with Lyme Disease (Credit: AFMC)

Some mice however appear to be immune to Lyme disease and according to MIT evolutionary biologist Kevin Esvelt that presents an opportunity. Dr. Esvelt has been experimenting with the mice, identifying the genes that provide the immunity. Dr. Esvelt now plans to use the gene-editing tool CRISPR to insert the immunity genes into the reproductive cells of the mice so that all of their offspring are born immune to Lyme disease.

Can altering the genes of Mice help to fight Lyme Disease? (Credit: NPR)

For field testing Dr. Esvelt has proposed releasing thousands of GMO mice onto some of the uninhabited islands off of Nantucket Island in the State of Massachusetts. It happens that Lyme disease is an epidemic on Nantucket; over 40% of the human population there has been infected, so the people of the island are more than ready to at least listen to Dr. Esvelt’s plan.

Now Dr. Esvelt is well aware of the possibility of unintended consequences, genetics and ecology are both very complex subjects after all. That’s what makes trying the plan on a small, uninhabited island first so attractive; the GMO mice will be confined until all of the ramifications have been studied. Only then, when not only Dr. Esvelt but all of the people of Nantucket are satisfied will the experiment move on to phase 2, releasing the mice onto Nantucket itself.

Plan for using GMO Mice to battle Lyme Disease on Nantucket (Credit: nMagazine.com)

In other words this is also a project that will take years before it can be called a success. Still, if the genetically modified mice do help to eradicate Lyme disease from the islands of Massachusetts then we will have another potent weapon in our fight against infections like Lyme disease.

Genetically Modified Foods (GMOs) are they the technology we need to feed our Growing Population? Or are they a Frankenstein Monster waiting to strike? Two stories that Illustrate the Promise and the Peril.

You hear about Genetically Modified Organisms every now and then on the news. Usually referred to as GMOs they are generating a great deal of excitement among biochemists and the food industry while causing just as much fear in some parts of the general population.

In a sense we have been modifying living creatures for 10,000 years. Starting with wolves we selectively bred them to enhance the characteristics we desired until we got man’s best friend the dog. Using the same techniques human beings have selectively bred hundreds of species of plant and animal to give us pretty much all of the food we, and our selectively bred pets, eat!

Selective breeding is genetic modification from the outside however. It’s only over the last 30-40 years that biochemists have been able to go straight to a living creature’s DNA and directly modify it. And it’s only in the past five years that scientists have possessed the precise and efficient gene-modifying tool known as CRISPR. (See my Posts of 5Aug17, 1Sept18 and 1Dec18 to learn more about CRISPR and how this gene-editing tool works).

How CRISPR Works (Credit: Genetic Literacy Project)

Using CRISPR biochemists hope to modify the plants and animals we eat in order to make them to grow larger more quickly, while requiring less fertilizer or feed. This would of course make food both cheaper and more abundant and in a world where more than 10% of the population goes to bed hungry that has to be a good thing.

One study could be a real game changer in the effort to produce more nourishing food. Researchers at the University of Illinois have been able to genetically modify the biochemical factories of plants in order to dramatically increase the efficiency of photosynthesis itself.

Production of Glucose by Photosynthesis (Credit: 19.eap-ing.de)

You’ll recall that photosynthesis is the chemical process by which plants use sunlight to convert carbon dioxide and water into sugars. In fact photosynthesis is the basic chemical reaction by which all of the world’s food is produced! Photosynthesis is rather inefficient however; it is chemically unable to distinguish between a carbon dioxide and oxygen molecules. According to plant biologist Donald Ort, the study’s senior author, “This is essentially anti-photosynthesis, and the plant produces a toxic compound that it has to recycle and detoxify.”

The researchers modified the DNA of Tobacco plants to simplify and speed up that detoxifying process resulting in plants that grew larger much more quickly, see image below. Dr. Ort and his team choose tobacco plants as a test subject because tobacco grows quickly and possesses genes that are easy to manipulate. The results are certainly impressive with tobacco plants that are 40% larger than ordinary plants.

Increased Growth of Tobacco Plants Achieved by Gene Editing (Credit: Clair Benjamin)

Having demonstrated the advantages of their approach the biochemists are now applying their technique to more useful plants like potatoes and soybeans. If this enhanced photosynthesis can be applied to other vegetable crops the resulting increase in food production could go a long way to helping feed the hungry nations of the world.

Some scientists are using gene editing to be a little more creative. One group wants to develop a spicy, peppery tomato. Now it turns out that tomatoes and peppers are pretty closely related, having split apart only about 20 million years ago. This means that the genes to produce Capsaicin, the chemical that makes peppers spicy, are still there inside a tomato’s DNA but according to co-author Agustin Zsögön they “are just not active.” Dr. Zsögön hopes to reactivate those genes allowing the humble tomato the ability to be as hot as any chilli pepper.

Can Gene Editing Produce a Spicy Tomato (Credit: Healthy Eating)

So why would scientists be so keen on developing a spicy tomato. Well the chemical capsaicin does more than just make your food taste spicy. Research has shown that capsaicin compounds are high in antioxidants; help the body fight cancerous tumors while aiding in both weight and pain management.

Right now the challenge is in determining which genes within the tomato to either turn back on, or turn off in order to get tomatoes to start producing capsaicin. Still, in a few years you may not need that habanero pepper in order to put some heat in your recipe for enchilada sauce!

Whether we use gene editing to greatly increase food production or just put a little more spice in our meals there are going to be people who are concerned about what other, unintentional chemicals we may be putting in what we eat. The workings of DNA, and the processes by which it controls the growth of cells are still largely unknown. The fear is that by modifying the genes of organisms to make them produce more food, we may also cause them to produce poisons or other deadly chemicals.

The scientists working on gene editing techniques are aware of this problem. As Dr. Ort says, “…any enhanced crops would undergo rigorous testing before they are ever consumed by humans.” Scientists like Dr. Ort may be determined to go slowly and test completely but what about large food corporations who are determined to both keep costs down and get their new products on the market before their competitors do. And not all the scientists are as trustworthy as Dr. Ort. Remember Chinese scientist He Jiankui who just two months ago revealed that he had used CRISPR on human embryos!

Dr. He defends his Research at the Genome Summit (Credit: BBC)

Like every advance in science gene editing can either benefit the world or harm it. It’s up to us, all of us to decide which it will be.

Gene Editing discovers a potential cure for Muscular Dystrophy, and a look back at the Jerry Lewis Telethon.

These next three days are celebrated as the Labour Day weekend here in the US and is also considered the unofficial end of summer. Back when I was growing up it was also the time of the Jerry Lewis telethon to benefit the fight against the disease Muscular Dystrophy (MD), a disorder that causes an almost total loss of strength and control of the muscles and is the leading genetic cause of death in children.

The Jerry Lewis Telethon began in 1966 and continued until 2010 (Credit: CBS)

Starting in 1966 and continuing until 2010 Jerry hosted the annual charity event which featured other celebrities and entertainment and which managed to raise $2.45 billion dollars for the study and treatment of MD. Despite the success of the telethon, and the large amount of money raised however MD has proven to be an intractable illness with little progress being made toward a treatment.

For those who aren’t familiar with MD it is a genetic disorder that prevents the production in the cells of the muscles of a shock absorbing protein called dystrophin. The lack of dystrophin causes the muscle cells to weaken and degenerate leading to a general failure of the bodies muscles. The first symptoms usually appear before a child is one year old.

Symptoms of MD (Credit: Pinterest)

Since MD is a genetic disorder it is not contagious but rather must be inherited from both parents, each of whom must carry a single recessive MD gene. Having a single MD gene does not cause the disease but by looking at the image below you can see how a man and woman, each of whom have one MD gene on their chromosome pair, can pass it on to their children.

Inheritance of a Recessive Genetic disorder such as MD (Credit: Human Illnesses)

Since a child gets one gene from each parent 25% get clean chromosomes from both parents, the child on the left. This child will not develop MD nor can it pass the mutated gene to its children. 50% of the offspring will get an MD gene from one parent but not the other; these are the two children in the middle. These children will not develop MD but carry the gene and can pass it on to their children just as they received it from their parents. Only the child on the right, the 25% who receive the MD gene from both parents, will actually develop the disease.

There has recently been some progress that offers a glimmer of hope in the fight against MD. The research was conducted on a family of dogs, King Charles Spaniels to be exact, who were found about ten years ago to also suffer from MD. The research used the new science of gene editing and in particular the gene cutting tool CRISPR that I discussed at some length in my post of 5Aug2018.

To put it simply CRISPR uses a virus, yes a virus to cut a section of DNA out of a chromosome with a cell and replace it with a different DNA section. The work was led by Eric Olsen at the University of Texas Southwestern Medical Center and consisted of using CRISPR to replace the mutated DNA in four one-month old male dogs.

CRISPR Working at the Molecular Level (Credit: Science)

Gene editing and CRISPR have been used before to treat other genetic disorders but MD was considered a long shot because the gene that manufactures dystrophin is the largest in the human genome and a large number of different mutations can lead to the disease. Still Dr. Olsen and his team injected the four dogs with millions of CRISPR viruses that were programmed to find and replace the mutated dystrophin gene.

The results were better than the researchers had expected. According to Dr. Olsen the dogs ‘…showed obvious signs of behavioral improvement…running, jumping…it was quite dramatic.”

Now this is only a test on four dogs, much more research will have to be carried out before any testing is conducted on humans. Still this is one more case where gene editing, and CRISPR in particular are giving us tools to fight diseases against which we once had no hope.

Which brings us to the ethical question. Changing the genes of a one-month old infant, dog or human, is playing god if anything is. And the technology that can ‘repair’ a child with MD can also create a ‘designer baby’ if that’s what we want.

As I said in my post of a little over a year ago my opinion is that we should move forward with gene editing but slowly, maintaining ethical controls on the research. I also that it is very important that we have a full-scale public debate now about how we as a society will regulate and control gene editing.

I’ve now told you my opinion, what’s yours?

Gene Editing in Humans: The Promise and the Peril

A collaboration of researchers at Oregon’s Health and Science University and the Salk Institute have carried out the first successful attempt at modifying the DNA inside human embryos. The team, led by Shoukhrat Mitalipov removed a genetic ‘mistake’ that causes a heart defect in humans from 42 out of 58 fertilized egg cells.

Doctor Mitalipov and his team used a gene editing technique known as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) to cut the DNA of the fertilized egg, remove the disease causing gene section and replace it with a healthy one. Chinese scientists had already attempted this technique several times but the CRISPR editing always resulted in a small number of editing ‘mistakes’ know as mosaicism and that when the fertilized cells began to divide to form an embryo not all of the cells received the edited correction. The picture below shows the CRISPR process being carried out on a fertilized human egg cell.

Gene Editing (Credit: Oregon Health and Science University)

In the paper Mitalipov and his team have published in the journal Nature their results indicate that they have succeeded in avoiding the errors in previous experiments. This is obviously of critical importance since any ‘off target’ results could easily cause more harm than good and the ethical controversy around gene editing is already a hot topic.

In order to avoid any such ethical concerns Mitalipov and his team only allowed the embryos in their study to develop for five days and there was never any intention of implanting the embryos into a womb. In fact any attempt to implant a gene edited human embryo into a womb is illegal in the US, Congress having forbidden the US Food and Drug administration from approving any such clinical trials.

When it comes to the technology of gene editing let’s face it, it’s only a matter of time before we can directly modify the DNA structure to suit our pleasure. If you think about it, we’ve been modifying the DNA of living creatures ever since we brought wolves into our caves and turned them into dogs but gene editing is a big leap forward and great harm could result from any carelessness.

Now anyone who has read some of my posts on this blogsite knows that I am pro-science and pro-technology. Also, the possible good that could be achieved by eliminating genetic disorders such as Hodgkin’s lymphoma, Huntington’s disease, the blood condition beta-thalassemia or Down’s syndrome or many others is just so great that we cannot simply refuse to try.

On the other hand, the possible harm that could occur to the children of gene editing experiments that resulted in ‘off target’ effects is simply horrible to consider. Any gene editing technique that we even consider employing on ourselves must be as perfect as is humanly possible before any clinical trials are attempted. In other words we have to do this slowly and carefully, making certain that the good will far outweigh any harm before proceeding.

I think most people can agree on such a policy. The possible rewards of gene editing are so great that we have to try, but slowly and carefully to avoid as many errors as we can. The real thorny ethical questions arise when we begin talking about using gene editing to ‘improve’ human beings, to create ‘designer babies’ rather than just to eliminate birth defects.

The problem is in finding any consensus on just what an ‘improvement’ might be, let alone on whose children will be ‘improved’. Now I’ve never been any good at telling people what is ethically right or wrong. However I will say this; each of us, wherever we live in this world, needs to consider this issue and make up our own mind!

Gene editing could very well become the most contentious issue of the 21st century and only an informed and thoughtful people can even hope to make the right choices. If you’d like to read more on the work at Oregon Health and Science University, the link below will take you to MIT’s Technology Review’s story.

https://www.technologyreview.com/s/608350/first-human-embryos-edited-in-us/