8 Dec 2017

Gene Therapy: Embryonic Engineering and the Future of Human Evolution

by L. E. Carmichael

Welcome to Part 3 of my series on gene therapy and genetic engineering. If you haven't already, I'd suggest reading Parts 1 and 2 before you continue:

Introduction to Gene Therapy: It Sounds Simple, But It's Sure Not Easy

Gene Therapy: Vectors, Viruses, and Why CRISPR Will Change Everything

Today, we're talking about the second major challenge with gene therapy - getting replacement DNA into EVERY affected cell in a patient's body - and why that problem leads to the central ethical debate in this field.

Who Are the Patients?

Gene therapy is designed for patients with genetic diseases. The word "patient" implies a couple of things. First of all, a child or adult that has multiple cells... hence the crux of the gene delivery problem we discussed earlier.

The second critical implication is that patients are autonomous human beings who are capable of understanding the treatment, including its risks and benefits, and are also capable giving their informed consent. Many genetic diseases strike during childhood, and in those cases, parents or guardians are legally permitted to give consent for their children's care.

Carry that thought to its logical extension, and it implies that parents could also have the right to consent to gene therapy on behalf of unborn babies - and specifically, single-celled embryos.

Embryonic Gene Therapy

In September, Chinese scientists announced that they had used CRISPR technology to edit a disease gene in human embryos. If those embryos had been implanted and allowed to develop, they would have been born as disease-free humans. It was an incredible breakthrough... and it opens up a lot of questions.

From a technological standpoint, embryonic gene therapy is absolutely the way to go:
  1. If you're doing gene therapy on a fertilized egg - by definition a single cell - the whole problem of delivering functional genes to every affected cell just goes away. Because "every" is now "one."
  2. Every cell in the eventual human body descends from that fertilized egg. So every cell in the human being that egg becomes carries the therapy gene. The cure is permanent.
  3. That human being's own eggs or sperm will also carry the functional gene. In other words, the cure is not just permanent, but heritable. It will be passed down to the person's own children, meaning one treatment could wipe out the disease from an entire future family tree.
Now We Know We Can... Does That Mean We Should?

The heritability of embryonic gene therapy is the reason that the vast majority of scientists have long considered such procedures unethical - or at the very least, warranting serious discussion. It is one thing to permanently alter the health of an existing human being - we've been doing that for centuries, using medical treatments as diverse as vaccines and surgeries. And indeed, if we have the power to improve someone's life and relieve their suffering, don't we have a moral obligation to at least try?

Altering the genomes of theoretical future humans is another thing entirely. First, because it's much harder to predict the consequences of actions on that scale, and second, because theoretical humans cannot consent to the alteration of their DNA when they do not yet exist. What right do we have to take those choices away? And while it's hard to imagine why someone would want to live with a disease when they didn't have to, our potential to impact the human genome, and therefore the course of human evolution, doesn't stop there.

After all, DNA is DNA. And CRISPR works on ALL the genes, not just the ones that can cause disease.

Embryonic Engineering and "Designer Babies"

Thanks to the Human Genome Project, we have a better understanding of our DNA than ever before. We're finding genes linked to all kinds of interesting traits, like eye colour and height and muscle development and intelligence...

Chinese scientists have genetically engineering dogs with over-developed musculature. Want your kid to be an Olympic power lifter, a soldier, a firefighter? Why bother building the necessary physique with diet and exercise when you could hard-wire their DNA? Ditto if you want your kid to get into Harvard or win a Nobel Prize.There have already been stories about parents undergoing IVF treatments who choose traits like the sex of their unborn child. With genetic engineering, the possibilities are truly becoming limitless.

The Ethics of Gene Therapy and Genomic Engineering

Just because a technology is potentially limitless, doesn't mean it has to be used to its full potential. We have an obligation to decide what uses of gene editing techniques are acceptable and what uses are not, and a further obligation to enforce whatever standards we agree upon.

The ethics of genetic engineering have been debated since the 1970s, when it became possible to manipulate DNA directly for the first time (before that, we had to do it the old fashioned way, using selective breeding). The debates will continue, and in light of these recent Chinese studies, likely intensify. And that's as it should be. Like so many technologies before them, gene therapy and genetic engineering have enormous potential for good, and enormous potential to be abused.

The choice will be up to us.

I hope you've enjoyed learning more about these topics, and I hope you'll continue following news reports about CRISPR and genetic engineering in the news. In the meantime, I'd love to know your thoughts on these issues. Please share and comment!

1 Dec 2017

Gene Therapy: Vectors, Viruses, and Why CRISPR Will Change Everything

by L. E. Carmichael

Welcome to Part 2 of my series on gene therapy! If you haven't already, I recommend that you read Part 1, Introduction to Gene Therapy: It Sounds Simple, But It's Sure Not Easy, before continuing with this post.

Ready? Here we go.

Viruses: FedEx For Genes

Gene therapy involves repairing or replacing a faulty gene that has led to disease. In order to do that, one major hurdle must be overcome: getting new DNA into the patient's cells. Cells, however, are designed to keep things out. That's why they have wrappers, called cell membranes. Scientists needed vectors: gene delivery systems capable of crossing the membrane.

In the early days of gene therapy research (by which I mean the 80s), the obvious way to cross the membrane was to use a virus. Viruses are highly efficient invaders - they have to be, because they are not capable of copying their own DNA. In other words, the only way a virus can reproduce and spread is to invade a host cell, hijack its equipment, and force the cell to package new viruses that can carry on the cycle of infection.

But what if scientists could replace some of the virus's DNA with a therapy gene? The virus would invade a patient's cells as per usual, but instead of causing infection, deliver some healthy human DNA. Sort of like molecular FedEx. Some viruses even contain DNA sequences that match sequences found in human DNA. These complementary sequences would prompt the host cell to incorporate the therapy gene into its own genome. Not only would the patient be cured, but the cure would be permanent.

What's that line about how it seemed like a good idea at the time?

The Problem With Viruses

For starters, they are viruses. The human immune system is designed to find and destroy viruses, before they invade the body's cells. This happens all the time, without our even realizing it. But sometimes, the immune system gets a little carried away.

That's exactly what happened to Jesse Gelsinger in 1999. The 18-year-old was part of a clinical trial of a gene therapy for a genetic disease known as OTC. When he received the treatment, his immune system had a massive over-reaction to the viral vector and began attacking his own cells. He died just a few days later.

The Other Problem With Viruses

Remember I said that some viruses can insert their own DNA - or therapy DNA - into the human genome, making a therapy permanent? Early gene therapy research occurred before we sequenced the entire human genome. Scientists didn't realize that complementary DNA sequences could occur in more than one location in a person's DNA... or that some of those locations were inside other genes. No good providing DNA to cure one genetic disease if your cure is going to knock out another gene. Especially if that gene helps to controls cell division... because uncontrolled cell division leads to cancer.

That's what happened to a number of young patients during an early clinical trial for the immune system deficiency SCID. And since those kids had compromised immune systems, they had no natural defences against the cancer their cure had created.

A Light at the End of the Tunnel

After these tragedies, scientists spent a lot of time searching for viral vectors that would NOT cause such horrific side effects. One type belongs to a family of viruses known as AAV. A gene therapy for Leber congenital amaurosis is built around AAV. It replaces a faulty gene in retina cells that causes children to go blind. And after decades of research, it looks as though this therapy will soon be available to the public. Developed by Spark Therapeutics, the treatment just received a unanimous endorsement from an FDA review panel, meaning approval for the therapy could be just around the corner - a literal light at the end of the tunnel for these patients.

So What is CRISPR, and Why Is Everyone So Excited About It?

A major downside of AAV viruses is that they do not incorporate their genetic package into the patient's existing genome. Which means they don't cause cancer, but also that the therapy gene can't be reliably passed on to daughter cells. That's OK for retinal cells, which don't divide. It's a lot less useful for treating diseases in other parts of the body.

CRISPR, on the other hand, works in all types of cells. It allows scientists to edit a patient's existing genes - correcting the typos that cause disease - and the changes are permanent. Here's how it works and why it's such a big deal.

Here's another really great video explaining CRISPR and its applications that unfortunately I was not able to embed.

And yes. You still have to get the components for CRISPR into the cell in the first place. One group of scientists has just found a way to do this without using viruses. They used gold particles instead.

As you can see, CRISPR could lead to incredible breakthroughs, and not just in gene therapy. But there are concerns as well. Stay tuned for Part 3, where I will explore what's perhaps the biggest one.

24 Nov 2017

Introduction to Gene Therapy: It Sounds Simple, But It's Sure Not Easy

by L. E. Carmichael

Muscular dystrophy, hemophilia, Leber congenital amaurosis (LCA), cancer... they all have one thing in common. They are genetic diseases, ultimately caused by missing or malfunctioning genes in the patient's DNA. Until recently, we could treat the symptoms of many genetic diseases, but not the causes. There was no way to reach inside a person's genes and repair the faulty code that started the whole problem.

Research into gene therapy aims to change that.

What is gene therapy?

Genes are blueprints for proteins. A complete set of working proteins makes a working human. In contrast, missing or malfunctioning proteins sometimes lead to disease. Many genes and proteins have to be affected to lead to diseases like cancer. Other diseases, like LCA and Lesch-Nyhan syndrome, result from a single broken gene.

The logic behind gene therapy is very simple: if a missing or malfunctioning gene is causing disease, a working copy of the gene could cure the patient. There are two ways to provide a working copy:
  1. Fix the gene that's already in the patient's DNA. This is easiest when the malfunction is caused by what's known as a "point mutation," which is basically a typo in the genetic code. Not all such typos are dangerous, but the right typo in the wrong place can knock out the entire gene.
  2. Provide a new copy of the entire gene. This strategy applies for genes with larger insertions - extra code - or deletions - missing code.
Once a working gene is present in the patient's cells, his or her body can make a functional protein... and in some cases, that may be enough to cure the disease.

That Does Sound Simple... So Why Is Gene Therapy So Hard?

Lots of reasons, but we're going to focus on two:
  1. Cells have lifespans. Dying cells are replaced by new cells, which are created by cell division. During this process, the cell's genome (all the DNA a person was born with) is copied so that each new daughter cell gets a complete set of instructions. There is no guarantee that a therapy gene that's simply floating around in the cell will end up in both daughters - to ensure that the shiny new gene will always be passed on, making the cure permanent, that gene has to become part of the original genome. Which means that, either
    1. the patient's original gene has to be edited in place, or
    2. the complete new gene has to embed itself into the patient's existing DNA.
  2. According to one estimate, there are 37.2 TRILLION cells in the human body. Not every disease affects every cell in the body. For example, LCA is a form of blindness caused by a faulty gene in the cells of the retina. To cure LCA, only retina cells would need to be treated. Far fewer than the whole 37.2 trillion, but still enough that getting a working gene into EVERY retinal cell is still a huge challenge.
So How Do Scientists Solve These Problems?

Stay tuned! In Part 2, I will explain what CRISPR is and why scientists are so excited about it. In Part 3, we'll tackle the "every cell" problem... and some awesome/scary breakthroughs that have recently hit the news.

In the meantime, you or your teenager might want to check out my YA science book, Gene Therapy. It's a couple years old now, but is still a solid introduction to the history and science of this cutting edge medicine.

10 Nov 2017

Who Writes for Science Centres and Museums, and How?

by Adrienne Montgomerie 

There are words everywhere at museums and science centres: on the walls, in the guide books, in their newsletters, blog posts, and marketing materials, in the visitor activities and kids’ clubs, and in the audio guides and press releases. And that’s just the stuff the public sees. Behind the scenes there are funding requests to write, reports, journal papers, and things like that.

Sci/Why wanted to know what it was like to work on those materials, so we asked some experts to tell us about it. What follows came out of interviews with three writers from Canada and the United States who specialize in writing for science centres and museums.

How Writers Write Content for Museums

The writers and editors don’t have to have all the knowledge, they just have to know where to find it. Sometimes they get to work with subject experts—scientists and researchers—one-on-one to gather info. Other times they read what experts wrote, to gather facts to share with the public.

“It’s really an exercise in cutting,” said Kimberly Moynahan, to make the expert knowledge fit on a very short panel. She works on exhibits for the likes of the Ontario and Saskatchewan science centres in Canada. Panels explaining exhibits can be super short. “A whole panel might be 60 words. And you’re going to explain fusion,” she said. “What really are the key messages? Everything you write has to add more information. You never repeat anything, because you don’t have room for that.”

“It’s super important to keep it fun,” Moynahan said. “We try to get kids to engage with other parts of the room or activities by challenging them with questions: Can you think of something bigger than an elephant? How many equilateral triangles do you see? Hint, look at the windows.

Imagine these panels on the wall beside an exhibit: “There’s a big header with question on it, then underneath that, a bold sentence with the secondary information. Beneath that, there might be one or two big sentences not quite as bold, then a paragraph of two to three sentences. A lot of people will only read the headers,” Moynahan explained.

Who the Museum Writers Target Audience Is 

When editing words the public will read, “I often have to eliminate a lot of jargon,” said Sara Scharf, editor in paleontology for materials at the Royal Ontario Museum in Canada. “I try to write for a grade 6 reading level or so.”

Aiming for that 11- or 12-year-old visitor is key, agrees Moynahan. “We might have some messaging for adults,” she said. “But the general audience for tone, language, and facts hit that middle school audience. That age group is the bulk of visitors—with schools coming through.”

Maggie Goodman is writing for younger kids (grades 3–5) because her work at the Chicago Museum of Science and Industry in the USA was for a science club as well as a summer program at the public libraries. “Language needs are very important when we’re looking through to make sure things work,” Goodman said. She also considers what kids are interested after 5 pm (outside of school hours).

The Museum Writers' Reference Shelf 

For the facts, the experts on the team are the writers’ most important resource. For the other parts, writers look to school curriculum (available online by province) to find words and ideas that are familiar to kids. Museums and science centres love to teach visitors new things. Knowing what the visitors might already be familiar with helps them build on and extend that knowledge, taking visitors from the familiar to the unfamiliar, and on to new reaches of knowledge. In the USA, Goodman refers to the Next Generation Science Standards that outlines the progression of scientific concepts and depth of understanding across the grade levels.

For checking the use and style of science jargon, writers ask their experts, and check books like Scientific Style and Format and AP Stylebook, and science dictionaries as well as standard school curriculum, and reputable websites. (Also see our article on science vocabulary by grade.)

The Museum Writers' Background 

Writers and editors working in a niche often know something about the topic beforehand, but sometimes their expertise is primarily in language. Scharf has a PhD in the history and philosophy of biology and Moynahan has a degree in zoology. Goodman has a background in educational development, but not in science. Sometimes not being a subject expert can help the editor or writer put themselves in the public’s shoes. They have to write materials that can be understood by visitors who are completely new to the subject, after all.

Moynahan says that her training as a scientist helps her a lot: “It’s helped our design team that I can do some of the research so they don’t have to farm it out. I already have a basic understanding and know what to Google. Most of the time, what you’re writing is not deep science. It’s very helpful to have a science background because you have to pull from three pages and get a story arc onto three [60-word] panels.” The scientists like working with her, she says, because “I can talk with research scientists who are truly expert in the field, and understand [them] enough that they don’t really have to explain [the science].”

What Museum Writers Want You to Know 

Moynahan wants others to know “the fact that it is a career path for a writer. It never occurred to me as a freelancer that there is work [for us in museums].”

“There is that false idea that there’s a gatekeeper to understanding science and liking science,” Goodman said. “We are really trying to tear that down at the Museum of Science and Industry. I’m really proud that there’s a universal ownership to science learning and exploration that’s occurring. Everybody has that on a daily basis, they’re just often not doing that in the terms that are used in a STEM [science, technology, engineering, and math] setting.”

“I like looking at the same material from multiple angles, helping to bring cutting-edge research to a broader audience,” Scharf said. “And the challenge of doing so in a variety of voices and registers.”

Do you remember an exhibit whose writing really stood out? Did you ever think about being on that creative team? Did you learn something when writing an exhibit that you’d like to share? Leave a comment and tell us about it.

5 Nov 2017

Nanotechnology: Corneal implants

By Simon Shapiro

A quick summary of how our eyes work: they refract (bend) light and focus it on the retina. The job of doing the refraction is split between the cornea and the lens. Two thirds of the refraction is done by the cornea, so it's critical in enabling vision. After light passes through the cornea, it passes through the pupil (in the centre of the iris) to reach the lens. Muscles in the eye (the ciliary muscle) can change the shape of the lens and allow the eye to focus nearer or further. The lens focuses light on the retina, which passes signals to the brain via the optic nerve.

It's all pretty neat, but some things can go wrong, especially as you get older. Common problems are that the lens and/or the cornea can become cloudy.

Cloudy lenses

When this happens to the lens, it's called a 'cataract'. Medical science has done an incredible job of fixing this problem. It sounds pretty radical and perhaps icky, but here's what ophthalmologists do: they make a tiny incision in the eye, suck the lens right out with a tiny 'vacuum cleaner', and put a plastic replacement lens in place. If you needed glasses before the surgery, the new lens will be the same prescription as your glasses and you won't need glasses after the operation. While it sounds complicated, the surgery takes less than 30 minutes and is done on an outpatient basis – no hospital stay is needed! Tens of millions of these operations are done every year, with a success rate of 98%.

Cloudy corneas

But when it's the cornea that gets cloudy, it's not that easy. It's possible to do a corneal transplant. A section of the cloudy cornea is removed, and replaced with a section of cornea from a donated eye from someone who has died. This surgery is much more difficult than cataract surgery, and of course it's dependent on having a suitable donor. Only tens of thousands of these operations are done, and the success rate is around 80-90%. More corneal replacements would be done, but there just aren't enough donated eyes.

So all of this means that a new idea for treating cloudy corneas is very exciting. Instead of transplanting human corneal tissue, a company called Corneat Vision has developed a synthetic cornea. The procedure is to remove a disc of the cloudy cornea and implant in its place a nanofiber 'skirt' with a clear lens at the centre. The skirt is made up of a sort of a nanofiber skeleton which corneal cells will grow into. The 'magic' of this device is the nanotechnology fiber and how cells grow right into the skeleton, making the implant really part of the eye.

Nanotechnology is becoming a very important field. It deals with particles ranging in size from 1-100 nanometers. A nanometer is one millionth of a meter. That's pretty small: a newspaper page is about 100,000 nanometers thick. When you get to the nano scale, materials start behaving differently, because you're getting to the scale of individual atoms and molecules. Atoms are about .1 - .5 nanometers in diameter, and molecules are over a nanometer across.  Finding out how materials behave differently on a nano scale and finding uses for that, is what makes the field so exciting.

More on nanoscience and nanotechnology in future blogs.

27 Oct 2017

Galapagos – From Blue-footed Boobies to Swimming with Sharks (Part 2)

By Margriet Ruurs

This is the second part of Margriet's story of her visit to the Galapagos Islands. Click here for the first part.
Blue-footed Boobie!

We hiked across Mosquera Islet seeing many birds up close, including – to my delight – the Blue-footed Boobie. We had watched documentaries about the Galapagos and were thrilled to see these birds in real life, as well as the bright red Sally Lightfoot Crabs scurrying across the black lava rocks, pelicans, swallowtail gulls, and many others.

Male Frigate Bird
One of the funnest animals was the sea lion. They look exactly like our North American seals, but the ears show that they are sea lions. It is amazing that all animals here have no fear of people. The seals come right at you, follow you like puppies, and want to play. It is the hardest thing not to reach out and pet them.

But this is a National Park and everything is highly protected. You cannot take a rock or a shell or touch anything. And rightly so.

Next we hiked North Seymour Island where the huge Frigate Birds soared overhead and young ones with white heads in perched in trees, looking like bald eagles.

Iguanas live on most islands but they are different species, having adapted to life on each island. Some islands had black iguanas; elsewhere they were yellow or even pink. We also saw the swimming ocean iguanas.

We hiked across Santa Fe and South Plaza islands. Being on a boat allowed us to visit more places but it also had the disadvantage of rocking and bobbing.

However, the biggest thrill for me was being able to swim off the back of the boat. Even after a few excited calls of “Shark!” I couldn’t figure out why it was okay to swim when there were sharks, but I trusted that our guides knew what they were doing.

We snorkeled several times, and it was beyond description to be in the ocean and have a large sea lion coming straight at me like a bullet, only to veer off at the last second. At one point two sea lions swam alongside me on either side. I watched turtles swimming below me, and hundreds and hundreds of colourful fishes like parrot fish.

And sharks. White tip sharks. Pretty cool.

On San Cristobal Island we strolled through the town and it was a bizarre experience to run into two friends from Kelowna!

We visited the Galapagos Interpretation Center. Sweat dripped of our bodies as we just stood still, reading about the violent human history on the islands. The animals really ought to be afraid of humans. They killed over 100,000 turtles and thousands of whales during the mid-1800s to mid-1900s. Nowadays, 97% of the islands is strictly protected as a National Park. All we can do is hope it will always stay this way and that Galapagos’s amazing variety of wildlife, which so well demonstrates its capacity to change and adapt to its natural environment, will be around for generations to come.

Reflecting back on it all, I am very glad to have been able to make this amazing trip and to see these special places on Earth. But it is a very long way to travel, expensive, and a bit overrated. Like ‘Serengeti’ the name ‘Galapagos’ has mysterious allure, but we have visited many places where plants and wildlife have adapted to their environment, and places like Australia’s Great Barrier Reef where we also saw giant tortoises and birds that stayed a foot away from us.

If you can go, do it. But otherwise, savour nature around you anywhere – nature is always incredible and forever adapting.

All photos are Copyright ©Margriet Ruurs

25 Oct 2017

Galapagos – From Blue-footed Boobies to Swimming with Sharks (Part 1)

By Margriet Ruurs

Margriet and Kees Ruurs start their Galapagos adventure.
Galapagos Islands: the very name conjures up images of a mysterious paradise, of unique species of animals that have adapted to their environment in special ways.

I am so glad and grateful that I had a chance to visit these faraway islands, even thought they have now lost some of their magic for me. But the intrigue has been replaced by memories of walking among iguanas and swimming with sharks and sea lions.

When we made the decision to travel to South America, there were two things high on our wish list: Easter Island and the Galapagos. I had read a wonderful, insightful book called Charles and Emma by Deborah Heiligman. This book heightened my wish to see these islands for myself.

We flew from Guayaquil, Ecuador, west across the Pacific and landed on one of the circa 40 Galapagos Islands (did you know there are so many islands here?!): Baltra. The humid heat hit us like a wall.

Tourists can travel to the Galapagos on their own or via a planned trip. But even if you go on your own, you cannot visit the National Park areas without a guide or small tour group. The Galapagos Islands are not only expensive to reach; they are expensive in every way, since all food and drink needs to come from far away.

A guide met us at the airport, expertly whisked our luggage away, and loaded us and about 18 others onto a bus. It was only a 10-minute drive to the boat launch where we climbed aboard a bobbing dinghy. We would repeat this exercise in agility many times in the coming days.

The dinghy brought us to a medium-sized yacht. The MV Coral I had about 14 cabins and a total of 20 guests on board plus a crew of 15, including two naturalists.

That first day we visited the Charles Darwin Station on Santa C,ruz Island. This is where the breeding program for the Galapagos Giant Tortoises takes place. Eggs from all over the islands are hatched here and the little Giant Tortoises (what do you call a little giant tortoise?) are raised until the age of five, when they are released in hopes that they will survive on their own.

We saw several huge, ancient tortoises as well as amazing prickly pear cactus trees that grow into huge trees over 400 years old. Unfortunately, the buildings were not open to the public and we did not see eggs or baby tortoises.

We walked through town and discovered that, like Easter Island, the Galapagos we had imagined was very different from reality. For instance, did you realize that the archipelago consists of nearly 40 islands, four of which are permanently inhabited?

And did you know that over 30,000 people live in Galapagos? I had no idea. The cities of Santa Cruz and San Cristobal have schools, stores, government buildings, and much more. Two airports serve the islands. Since Galapagos was used as a penal colony by Ecuador, most houses had bars and gates as opposed by the much more friendly atmosphere on Easter Island. The heat was incredible.

There is almost no rain on these lava islands. Some are lush and green, but others are a volcanic wasteland. In fact, one early explorer wrote home to describe that he had arrived in what he truly thought was hell!

That first night we slept well in our slightly rocking bunks. However, the next two nights were rough as we crossed open ocean and coped with high swells that rocked the small boat left to right and front to back. Things flew through the cabin, and we ended up sleeping on the outside deck. Most of us didn’t get sea sick, but we rocked for three days afterwards.

(To be continued....)

All photos are Copyright ©Margriet Ruurs

For Margriet's previous blog posts about her visit to Rapa Nui, also known as Easter Island, click here and here.