#Knoepfler book

[pknoepfl]

How to Build a Dragon or Die Trying: check out new book with my daughter Julie

How to Build a Dragon or Die Trying: check out new book with my daughter Julie

My daughter Julie and I have written a book together entitled,  “How to Build a Dragon or Die Trying, A satirical look at cutting edge science.”

The book will be out sometime in June most likely.

This is a very different kind of book than my first two, Stem Cells: An Insider’s Guide and GMO Sapiens.

In How to Build a Dragonwe, first of all, take a satirical tone as highlighted by the subtitle. We…

[biomedgrid]

Biomed Grid | What should be our community’s Responsibility?

Opinion

Nearly everyone in the various fields of Bio Medical research is aware of emerging gene editing tools developed round the CRISPR-Cap9 system. What seems less clear, is now fully involved in the discussions of the associated ethical and societal issues is this research community. This is needed not just in the education of our students and other mentored, but with the general public. The importance of this is readily seen in the diversity of published opinions on both the utility of and implications of these new gene editing tools. For example, in the book “GMO Sapiens” by Paul Knoepfler and with Nature’s [1] headlines: “Russian biologist plans more CRISPR-edited babies” scary views are being presented. In April 2019 the ScienceDaily news section [2] announced that Cornell University scientists used for the first time in human cells a new type of gene CRISPR system, which can erase large stretches of DNA, thus expanding the potential of gene editing. Recently the John Hopkins school of medicine Public Health magazine, featured a broader based forum discussion: “Should CRISPR be used to edit human genes to treat genetic diseases?” [3].

So, what does all of this suggest about our need, as biomedical researches, to be involved in discussions of the associated ethical and societal issues. First of all, there is a general lack of understand of some important facts. These include some basic genetic knowledge: such as the fundamental distinction between somatic and germ line cells; the long history of genome modification via domestications; and the degree of the complexity of multi gene networks and interactions. These are in addition to the fact that inherited genetic diseases fall into at least two distinct categories. In particular, there are those that arise from common single gene mutations, and those that do not. These single defective gene cases include many cancers and some lifelong disabilities, such a Sickle Cell and Cystic Fibrosis. How while the potential to improve human life in such cases with gene editing seems obvious, it is nearly as obvious, that there are still issues and the potential for misuses [4-6].

An obvious issue, even with editing to a fix common single gene inherited mutations, is whether can it be done without germ line effects. This is in itself not simple. Note, the use of Pre-implantation genetic diagnosis (PGD) of an early embryo, for rejection if carrying the mutation. This is currently available to parents who feel strongly that they have an obligation to not to pass on, clearly understood defective disease genes to their children. Importantly PGD results in a changed the germ line! Thus, for some this is a mixed ethical problem, should they edit their own reproductive defective cell lines or select against a defective embryo. Such issues for many can becomes religious or moral issues.

Then there are those multiple defective gene cases. These raise additional issues. Some are technical, do we have tools for simultaneously or sequentially editing multiple sites. Do we even understand all of the defects or even their interplay with other genetic processes? The answers to all of these is currently no. Note, these are closely related to the larger gene editing ethical and societal issue: augmenting by editing our genes, for potential improvements affecting our future! Clearly in the case of enhancement gene editing, there is a clear general agreement, against among most medical ethicists, and current geneticists. Our ignorance of the full implications of such, is the obvious reason. We surely do not even understand the full complexity of the interactions between many different genetic networks let along their interactions with our current varying environments, to say nothing of the future. A useful analogy here is that of the automobile: normally when a good running car breaks down, your mechanic will fine a single part that needs fitting or replacement; however if you were to ask your mechanic to upgrade your VW or Ford to drive like a Ferrari, outside of thinking you were a bit crazy, he would note a require for complete understanding of how all your car’s systems now work and how the upgraded enchantments might interact with them.

Now as members of the biomedical community we generally understand the great health potential of these new tools and both their limitation and potential of misuse, thus we have a responsibility to be part of the discussions and to help with the education of the issues involved. Many universities and medical schools are currently not providing comprehensive coverage or general education of these complex issues. This is part due by not understanding the lack of public trust in science, coupled with the sense felt by many that we are playing “god”. This latter requires real collaborative efforts, involving many disciplines and a sense of history. That history includes human kinds long involvement in germ line modification in animals and plants for domestication, as well as in our very acts of mate selection. History includes the fact that (evolution) biology is a historical science, with all the complexities of dependence on the full historical time sequence.

Read More About this Article:https://biomedgrid.com/fulltext/volume4/what-should-be-our-communitys-responsibility.000742.php

For more about: Journals on Biomedical Science :Biomed Grid

[liliannorman]

What would it take to make a unicorn?

The unicorns in the new movie Onward may look like the beauties that adorn fanciful clothing and school supplies. But don’t be fooled by their silvery white color and shimmery horns. These gussied-up ponies act like dumpster-diving raccoons while snarling at residents. They roam the streets of Mushroomton, a town populated by magical creatures.

The unicorns popular today typically aren’t garbage-eating pests. But they often have a similar look: white horses with heads that have sprouted a single spiraling horn. While everyone knows that these unicorns are just a flight of fancy, is there any chance they could ever exist?

The short answer: It’s highly unlikely. But scientists have ideas about how these animals could become real. A bigger question, though, is whether it would be a good idea to make one.

The long road to a unicorn

A unicorn doesn’t look that much different from a white horse. And getting a white horse is pretty easy. One mutation on a single gene turns an animal into an albino. These animals don’t make the pigment melanin. Albino horses have white bodies and manes and light eyes. But this mutation can also mess with other processes inside the body. In some animals, it can lead to poor vision or even blindness. So unicorns that evolved from albino horses might not be all that healthy. 

Maybe unicorns could evolve from albino horses. These animals lack the pigment melanin. That leaves them with white bodies and light eyes. Zuzule/iStock/Getty Images Plus

A horn or rainbow coloring are more complex traits. They tend to involve more than one gene. “We can’t say ‘we are going to change this gene and now we’re going to have a horn,’” says Alisa Vershinina. She studies the DNA of ancient horses at the University of California, Santa Cruz. 

If any of these traits were to evolve, they would need to give a unicorn some advantage that helps it survive or reproduce. A horn, for instance, might help a unicorn defend itself against predators. Colorful features might help a male unicorn attract a mate. That’s why many birds have bright and bold colors. “Maybe horses would be able develop these crazy colors … that would favor boys that are very beautiful pink and purple,” Vershinina says.

But none of this would happen fast because horses (and the resulting unicorns) have relatively long lifespans and reproduce slowly. Evolution “doesn’t work in a snap,” Vershinina notes. 

Insects generally have short generation times, so they can evolve body parts quickly. Some beetles have horns that they use for defense. A beetle might be able to evolve such a horn in 20 years, Vershinina says. But even if it were possible for a horse to evolve into a unicorn, that “would take more than a hundred years, probably, if not a thousand,” she says. 

Fast-tracking a unicorn

Perhaps instead of waiting for evolution to make a unicorn, people could engineer them. Scientists might use the tools of bioengineering to cobble together the traits of a unicorn from other creatures. 

Paul Knoepfler is a biologist and stem-cell researcher at the University of California, Davis. He and his daughter Julie wrote a book, How to Build a Dragon or Die Trying. In it, they ponder how modern techniques could be used to build mythical creatures, including unicorns. To transform a horse into a unicorn, you could try adding a horn from a related animal, Paul Knoepfler says. 

dottedhippo/iStock/Getty Images Plus

A narwhal’s tusk looks like a unicorn horn, but it’s actually a tooth that grows in a long straight spiral. It grows through a narwhal’s upper lip. That might make it tricky to successfully put one on a horse’s head, says Paul Knoepfler. It’s not clear how a horse could grow something similar, he says. If it could, it might get infected or damage the animal’s brain.

One approach would be to use CRISPR. This gene-editing tool lets scientists tweak an organism’s DNA. Researchers have found certain genes that are turned off or on when animals are growing their horns. So in a horse, “you might be able to … add a few different genes that would result in a horn sprouting on their head,” he says.

Explainer: What are genes?

It would take some work to figure out which genes are the best to edit, Knoepfler notes. And then there are challenges to making the horn grow properly. Also, CRISPR itself isn’t perfect. If CRISPR creates the wrong mutation, this could give the horse an unwanted trait. Maybe “instead of the horn off the top of its head, there’s a tail growing there,” he says. A change that drastic, though, would be pretty unlikely. 

A different approach would be to create an animal that contains DNA from several species. You might start with a horse embryo, Knoepfler says. As it develops, “you might be able to transplant some tissue from an antelope or some animal that naturally has a horn.” But there’s a risk that the horse’s immune system might reject the other animal’s tissue. 

Explainer: How CRISPR works

With all these methods, “there’s a lot of things that could go wrong,” Knoepfler notes. Still, he says, making a unicorn seems almost realistic compared with creating a dragon. And for any approach, you’d need a team of researchers, plus veterinarians and reproductive experts. Such a project would take years, he notes. 

The ethics of making a unicorn

If scientists succeed in giving a horse a horn, it might not be good for the animal. Vershinina questions whether a horse’s body could support a long horn. A horn might make it harder for a horse to eat. Horses haven’t evolved to deal with a horn’s weight as some other animals have. “Rhinos have this awesome horn on their head. But they also have a massive head and they can eat with it,” she notes. “This is because this horn evolved as a part of the body.”

There are many other potential problems. Lab-grown unicorns would never have existed as part of an ecosystem. If they entered the wild, we have no clue what would happen and how they would interact with other species, Knoepfler says. 

Cartoon unicorns sometimes sport vivid rainbow manes. “To have something like a rainbow, it’s got to take tons of genes interacting in a very interesting way,” Alisa Vershinina says.ddraw/iStock/Getty Images Plus

Also, huge ethical questions surround the possibility of modifying animals or creating something like a new species. The purpose for creating these unicorns would matter, argues Knoepfler. “We’d want these new creatures to have happy lives and not suffer,” he says. That might not happen if they were being bred like circus animals just to make money.

Vershinina has considered the ethics of trying to recreate creatures, such as mammoths, that don’t exist anymore. One question that would apply to unicorns and mammoths alike is how such an animal might survive in an environment to which it’s not adapted. “Are we going to be solely responsible for keeping it alive and feeding it?” she asks. Is it OK to make just one, or does a unicorn need others of its kind? And what happens if the process isn’t successful — will those creatures suffer? Ultimately, “who are we on this planet to play this role?” she asks. 

And what if unicorns aren’t the sparkly, happy creatures of our fantasies? “What if we did all this work and we have these beautiful perfect unicorns with rainbow manes and these perfect horns, but they’re very grumpy?” Knoepfler asks. They could be destructive, he says. They might even turn out to pests, like the ones in Onward.

The origins of the unicorn myth

The earliest description of something like a unicorn comes from the fifth century B.C., says Adrienne Mayor. She’s a historian of ancient science. She works at Stanford University in California. The description is found in the writings of the ancient Greek historian Herodotus. He wrote about the animals of Africa. 

“It’s pretty clear that [his unicorn] would have been a rhinoceros. But in ancient Greece, they would have had no idea what it actually looked like,” Mayor says. Herodotus’ description was based on hearsay, travelers’ tales and a heavy dose of folklore, she says.

The image of a horned white horse comes later, from Europe in the Middle Ages. That’s from about 500 to 1500 A.D. Back then, Europeans didn’t know about rhinos. Instead, they had this “enchanting image of a pure white unicorn,” Mayor says. In this period, unicorns were also a symbol in religion. They represented purity.  

At that time, people believed unicorn horns had magical and medicinal qualities, Mayor notes. Shops that sold medicinal compounds would sell unicorn horns. Those “unicorn horns” were actually narwhal tusks collected at sea. 

What would it take to make a unicorn? published first on https://triviaqaweb.tumblr.com/

[geneticallymodified]

The Future in Designer Humans

Since the discovery of the DNA, scientists were catalyzed to study more about genetics and advance the technology in genetic research. As time passed and more discoveries were made, the idea of genetically designing a human became more and more plausible. Physical and behavioral traits could be altered to fit a certain aesthetic by parents wanting a child. Undoubtedly, many people condemn the idea and argue that picking out certain traits for your kid to have is immoral and unnatural. Yet, some people change their minds when they're told the process can also make sure their child will not get any life-altering inherited diseases such as cancer. Even if genetic engineering was regulated and limited by the government for health concerns, it’s not just the child and their offsprings that will be affected. Regardless of unethical implications many see now, modifying human genomes could be the next step in human evolution to create healthier human beings with longer life-spans.

While the concept of designing human genes seems like something out of a science fiction novel, it was only recently made possible through the introduction of CRISPR-Cas9 microbial adaptive immune system, a gene editing tool found in some bacteria to help fight against viruses. According to Paul Knoepfler, a professor in cell biology who gave a TedTalk about designer babies, “[CRISPR is] like a genetic swiss army knife… and one of the tools is kind of like a magnifying glass or a GPS for our DNA,” (Knoepfler). The technology makes it possible to find certain genes a lot quicker as well as to manipulate it for more precise results. "Overnight the cost of engineering have shrunk by 99 percent. Instead of a year, it takes a few weeks to conduct experiments,” says YouTuber, Kurzgesagt on an informative video about genetic engineering (Genetic). This big breakthrough gives scientists the ability to research on what parts of the genome affect what behavioral or physical attribute using less money without taking up as much time.

Furthermore, genetic engineering can already be seen in humans that went through the mitochondrial DNA replacement therapy. This operation consists of taking the nuclear material from the mother’s diseased embryo and putting it inside a healthy and empty egg from a donor; thus creating a descendent of the mother, the father, and the donor of the mitochondrial DNA. Marcy Darnovsky writes in a New York Times article that about one to four thousand children develop a mitochondrial disease, passed down from their mother, that inhibits the mitochondria from converting nutrients from food to energy for the body (Darnovsky). The procedure makes it possible for women with a mitochondrial genetic disorder that want to have biological children be able to carry without their child inheriting and suffering from the disease. In addition, in vitro fertilization and gene therapy are a few other techniques that doctors use for higher possibilities in prospective parents to actually conceive and have a child. Without these technologies many parents would not be able to have their beloved child/children.

However, while there are many concerns about the longevity and the unpredictability of DNA manipulation, there’s no other way to get clear results than to start the study. Paul Knoepfler expresses his concern that “[w]e should not allow creating genetically modified people, because it's just too dangerous and too unpredictable” (Knoepfler). He says that there is still so much we don’t know about the long term effects of CRISPR that if we do get rid of an inherited disorder in a child, we may end up making them more aggressive or generate a hidden undesirable trait. While I agree that as much research should be done on animals with a similar genetic makeup before trying them on humans is the smartest way to go, there’s only so much we can learn from these other species. According to Pang and Ho, authors of the scientific article regarding the scientific process of designer babies, the flaw with these procedures is that the genetic changes are inheritable and the effects can only be analyzed through a longitudinal study in the generations produced by the modified human (Pang). Even if a study on the effects start now, sufficient data won’t be made until several life spans later, which is why it should start as soon as it is made safe by scientists.

In addition, this idea has been compared to eugenics and selective breeding. Since the horrific events that happened in the 1900’s in both the United States and England, the word “eugenics” now has bad connotations and rightfully so. Sonia Suter, author of “A Brave New World of Designer Babies,” challenges the idea that eugenics is not as evil as everyone conveys it out to be. Suter says that even though it was made with a respectable purpose to improve the human race, the way it was executed in the 1900’s includes “underlying racism and class biases, reinforcement of social inequalities, and threats against democracy” (Suter, 912). The difference with old eugenics and this new and improved “eugenics” is that it is through individual practices and not done to particular groups of people. Instead of one person controlling others on their actions, it will be their own choice to have a genetically modified child.

Furthermore, people fear the inherent social division that may come with it but don’t realize these fears are common when there is a transition from one stage to the other. “ If each step [regarding genetic engineering] were to get the same scrutiny that mitochondrial replacement therapy got, genetically modified humans could become as normal as genetically modified crops and bacteria are today—and, barring the occasional controversy, as widely accepted” write Akshat Rathi in his article about designing humans (Rathi).  People are always sceptical and fearful of the unknown and anxiety towards what might happen, but we have always found a way to make it work and we have found ways to survive. “Science fiction became our reality and we don’t even think about it,” says Kurzgesagt in his video (Genetic).  Looking back at the past, many people were scared of science; then they were scared of technology. Society made books, pictures, and articles that expressed their concern, but these things are big parts of our lives now and hard to live without.

Genetic modifications can open the door to many great opportunities for humans in the future. With this, scientists can figure out ways for humans to be immune to cancer and other inheritable diseases such as schizophrenia and HIV/AIDs so it does not affect the child or the future generations they may produce. However, with unpredictable science such as this, there is still a lot more research to be done before human trials. As said by the professors in the article about designer babies, “while the procedures should not be considered to be ready for clinical applications, research should continue to improve the technology and to assess the long term safety of these procedures.” (Pang). It’s understandable to be wary of what may come with something that is unknown, but disregarding the research altogether would not be a smart move.

[galeridergame-blog]

In article from the Los Angeles Times' Leila Miller, father-daughter team Paul and Julie Knoepfler take a theoretical look at how gene editing could build a creature very much like a #dragon. 

[thrivous]

"We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer," said FDA Commissioner Scott Gottlieb, referring to the "historic" approval of the first gene therapy in the US (see below), adding that new technologies such as gene and cell therapies could transform medicine. "With the approval of Kymriah, we are once again delivering on our commitment to change the course of cancer care," said Novartis CEO Joseph Jimenez.

Kymriah is based on Chimeric Antigen Receptor T (CAR-T) cells, immune T cells modified with engineered receptors, also featured in other spectacular research news released last week.

There is, however, a catch: Novartis priced the drug at $475,000 for one treatment, Bloomberg reports, “well below even higher expectations of up to $700,000.”

This raises ethical concerns. Of course, drug development costs money, and a private company like Novartis is entitled to recover costs and make a profit. But, in the US, the FDA approval process itself adds billions of dollars to drug development costs. Therefore, it could be argued that suffering US patients are ultimately required to pay hundreds of thousands of dollars each to support inefficient regulation.

In related news, Peter Thiel and other libertarian investors are funding an offshore human clinical trial of a herpes vaccine, “skirting FDA regulations and sparking a heated debate over US safety rules,” as reported by TechCrunch. As usual, facts play a very minor role in the heated and heavily politicized debate, but a Reason article tries to at least get the facts right.

Futurism reports that scientists at the Albert Einstein College of Medicine claim that they have discovered the maximum lifespan of human beings, which is about 125 years. But the “cut-and-paste” CRISPR gene editing technique “is making it possible to modify DNA, the source code of life itself,” which may allow us to extend that maximum lifespan.

See also Pulse 22 for a review of the recently published book, A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution, co-authored by Jennifer Doudna, one of the inventors of CRISPR, and the recent AMA (Ask Me Anything) session hosted by CRISPR researcher Paul Knoepfler, Professor at UC Davis, on Reddit.

First gene therapy approved by the FDA, officially available in the US. The US Food and Drug Administration (FDA) has approved Kymriah, a Chimeric Antigen Receptor T cell (CAR-T) therapy, which becomes the first gene therapy officially available in the United States. Kymriah (tisagenlecleucel), from Novartis, has been approved for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL).

First response of central nervous system tumor to CAR T-cell therapy. Scientists at Massachusetts General Hospital (MGH) have found a remarkable treatment response in a patient participating in a clinical trial of an investigational CAR T-cell therapy. The research results, published in New England Journal of Medicine, indicate that the treatment induced complete remission of a brain metastasis of the difficult-to-treat tumor diffuse large-B-cell lymphoma (DLBCL), which had become resistant to chemotherapy. This is the first report of a response to CAR T-cells in a central nervous system lymphoma.

Single-molecule nanomachines penetrate cell membranes to heal or kill cells. Researchers at Rice University, North Carolina State University and Durham University have developed motorized single-molecule nanomachines, driven by light, able to penetrate the membranes of individual cells, either bringing therapeutic agents into the cells or directly inducing the cells to die. The study, published in Nature, describes how the scientists created several different light-activated motorized molecules designed to home in on specific cells, drill through cellular membranes using their molecular-scale nanomechanical action, induce necrosis, and introduce chemical species into live cells. The researchers expect that molecular machines could eventually also be used in live subjects.

Nanoparticles deliver mRNA to cells for ‘hit-and-run’ gene therapy. Scientists at Fred Hutchinson Cancer Research Center have used nanoparticles to deliver transient gene changes to targeted cells. A study published in Nature Communications describes a nanoparticle delivery system to extend the therapeutic potential of messenger RNA (mRNA), which delivers molecular instructions from DNA to cells in the body, directing them to make proteins to prevent or fight disease. According to the scientists, their method could someday make “hit-and-run” gene therapy feasible around the world, even in areas with little or none of the specialized technology now needed to genetically engineer cells.

DNA nanoparticles permit analyzing how neurons work. Researchers at the University of Chicago have developed a way to use nanopackages made out of DNA to deliver a payload of tiny molecules directly into a cell. DNA is a suitable material because it can dissolve harmlessly once its purpose is achieved and, like LEGO, it has standard interlocking pieces that make it easy to build into configurations. The research results, published in Nature Nanotechnology, describe how the technique permits analyzing the fast interaction between neurons and neurosteroids, chemical messengers that play a key role in the brain.

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Originally published at thrivous.com on September 04, 2017 at 12:20PM.

[pknoepfl]

Find $250 Easter egg in GMO Sapiens #CRISPR book: here's a hint

Find $250 Easter egg in GMO Sapiens #CRISPR book: here’s a hint

Want $250 as well as at least a sliver of science-related glory?

Within my book GMO Sapiens on CRISPR and human genetic modification, I’ve hidden a scientific Easter egg.

There’s more Easter egg info over here including the rules.

If you are the first one to find and properly explain this egg to me after buying the book, you win $250. I had originally limited it to the print edition, but…

[pknoepfl]

Ou dragon book gets a flaming thumbs up in Nature review

Ou dragon book gets a flaming thumbs up in Nature review

A three-headed dragon statue in Russia, an image from our book from Shutterstock.

When you write a book like our new dragon book, as the first reviews of it start coming in you just never know what they’ll be like.

When the person or outlet doing the review has a huge audience, the stakes are higher.

How have the early reviews been for our new How to Build a Dragon or Die Trying book?

For…

[pknoepfl]

Context for my Nature piece on redefining "gene edit" to be more precise

Context for my Nature piece on redefining “gene edit” to be more precise

When I say “gene edit” or “genome editing”, what’s the first thing that pops in your mind?

CRISPR gene edit vs mutation. Analogy to editing a book with a scalpel. Photo Paul Knoepfler

It will depend on who you are.

For many lay people until a few weeks ago when the world heard about He Jiankui‘s claim of CRISPR’d babies they may not have had anything pop in their heads when hearing “gene…

[pknoepfl]

Hint for $250 Easter egg in GMO Sapiens #CRISPR book

Hint for $250 Easter egg in GMO Sapiens #CRISPR book

Want $250 as well as at least a sliver of science-related glory?

Within my new book GMO Sapiens on CRISPR and human genetic modification, I’ve hidden a scientific Easter egg.

There’s more Easter egg info over here including the rules.

If you are the first one to find and properly explain this egg to me after buying the book, you win $250. I had originally limited it to the print edition, but…

[pknoepfl]

To stem cell clinics: do your homework & take FDA "current thinking" seriously

To stem cell clinics: do your homework & take FDA “current thinking” seriously

One of the difficult things about the regulatory sphere that covers stem cells in the US is that many aspects are confusing or puzzling both to the public and so-called experts. We’ve been talking through some of the questions that come up in this area in posts and comments on this blog.

What does a warning letter really mean? What triggers it?

Why do some businesses selling stem cells get…

[pknoepfl]

Stem Cell Talk & Book Signing Tomorrow October 5 at Noon in Sacramento

Tomorrow at lunch time I’ll be giving a talk on stem cells, taking questions, and signing copies of…

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[pknoepfl]

More on my new stem cell book & how to get 30% off

I’m excited about a new development on my stem cell book.

It should be available on Amazon in…

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[pknoepfl]

Stem Cells: An Insider's Guide Book Signing & Talk on October 10th

Somewhere out in the ocean there is a container ship steaming from Singapore here to the US and…

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