Genetic Engineering

What if we could cure people of inherited diseases before they were born?

From Pioneering Stem Cell Trial Seeks to Cure Babies Before Birth

Elianna has a rare inherited blood disorder called alpha thalassemia major, which prevents her red blood cells from forming properly. The disease, which has no cure, is usually fatal for a developing fetus.

But while still in her mother’s womb, Elianna received a highly daring treatment. Doctors isolated healthy blood stem cells from her mother and injected them through a blood vessel that runs down the umbilical cord. Four months later, Elianna was born with a loud cry and a glistening head of hair, defying all medical odds.

Elianna is the first in a pioneering clinical trial that pushes the boundaries of stem cell transplants.


The idea that you can treat a fetus while inside a mother’s womb is pretty radical. Doctors have long thought that fetuses are encased in an impermeable protected barrier, which helps protect the developing human from outside insults.

Early experiments with fetal stem cell transplants seemed to support the dogma. Most trials using the father’s stem cells failed, leading doctors to believe that the procedure couldn’t be done.

But subsequent research in animals discovered a crucial tidbit of information: the mother’s immune system, not the fetus, was rejecting the father’s stem cells.

There’s more: rather than being quarantined, fetuses continuously exchange cells with their mothers, so much so that fetal cells can actually be isolated from a mother’s bloodstream.

The reason for this is to quiet both parties’ immune systems. Because the fetus has part of the father’s DNA, it makes a portion of their cells foreign to the mother. This back-and-forth trafficking of cells “teaches” both the mom’s and the fetal immune system to calm down: even though the cells aren’t a complete genetic match, the fetuses’ cells will tolerate their mother’s cells, and vice-versa. In this way, during pregnancy the fetal immune system is on hold against the mother.

This harmonious truce changes once the baby is born. The child’s immune system grinds into action, attacking any cells that are foreign to its body. Once born, a bone marrow transplant requires drugs to kill off the infant’s own bone marrow cells and make room for healthy ones. It also requires high doses of immunosuppressant drugs to keep the infant’s immune system at bay while the new, healthy cells do their job.

Someday, maybe, we could regrow limbs

From Axolotl Genome Slowly Yields Secrets of Limb Regrowth | Quanta Magazine

Salamanders are champions at regenerating lost body parts. A flatworm called a planarian can grow back its entire body from a speck of tissue, but it is a very small, simple creature. Zebra fish can regrow their tails throughout their lives. Humans, along with other mammals, can regenerate lost limb buds as embryos. As young children, we can regrow our fingertips; mice can still do this as adults. But salamanders stand out as the only vertebrates that can replace complex body parts that are lost at any age, which is why researchers seeking answers about regeneration have so often turned to them.

While researchers studying animals like mice and flies progressed into the genomic age, however, those working on axolotls were left behind. One obstacle was that axolotls live longer and mature more slowly than most lab animals, which makes them cumbersome subjects for genetics experiments. Worse, the axolotl’s enormous and repetitive genome stubbornly resisted sequencing.

Then a European research team overcame the hurdles and finally published a full genetic sequence for the laboratory axolotl earlier this year. That accomplishment could change everything.

“The genome was a huge problem that had been lingering over the heads of everyone working in axolotl,” said Jessica Whited, the assistant professor and researcher who supervises this laboratory at Harvard Medical School and Brigham and Women’s Hospital. Now that she and other researchers have the whole axolotl genome, they’re hoping to unlock secrets of regeneration and perhaps even to learn how humans could harness this power for ourselves


After an amputation, a salamander bleeds very little and seals off the wound within hours. Cells then migrate to the wound site and form a blob called a blastema. Most of these recruits seem to be cells from nearby that have turned back their own internal clocks to an unspecialized or “dedifferentiated” state more like that seen in embryos. But it’s unclear whether and to what extent the animal also calls on reserves of stem cells, the class of undifferentiated cells that organisms maintain to help with healing. Whatever their origin, the blastema cells redifferentiate into new bone, muscle and other tissues. A perfect new limb forms in miniature, then enlarges to the exact right size for its owner.

Scientists don’t know whether axolotls use the same mechanisms to regenerate their internal organs as their limbs. They also don’t know why an axolotl can grow back an arm many times in a row but not indefinitely — after being amputated five times, most axolotl limbs stop coming back. Another mystery is how a limb knows to stop growing when it reaches the right size.


Monaghan is studying axolotl retinas to try to improve the outcomes of prospective stem cell therapies in aging human eyes. He also thinks finding out how axolotls rapidly regrow their lungs could help us learn to heal human lungs, which naturally have some regenerative power.

McCusker has studied how the tissue environment of a salamander’s regenerating limb controls the behavior of cells. Someday, we might be able to regulate the environment around a cancer cell and force it to behave normally.

CRISPR pioneers now use it to detect infections like HPV, dengue, and Zika

From New CRISPR tools can detect infections like HPV, dengue, and Zika – The Verge

The new tools, developed by the labs of CRISPR pioneers Jennifer Doudna and Feng Zhang, are showcased in two studies published today in the journal Science. In one paper, Doudna’s team describes a system called DETECTR, which can accurately identify different types of the HPV virus in human samples. In the second paper, Zhang’s team shows an upgraded version of SHERLOCK — which was shown last year to detect viruses like Zika and dengue, as well as other harmful bacteria — in human samples.


The CRISPR used in the first Science study is called CRISPR-Cas12a. Doudna’s team discovered that when this type of CRISPR snips double-stranded DNA, it does something interesting: it starts shredding single-stranded DNA as well

the CRISPR system is programmed to detect the HPV DNA inside a person’s cells. When CRISPR detects it, it also cuts a “reporter molecule” with single-stranded DNA that releases a fluorescent signal. So if the cells are infected with HPV, scientists are able to see the signal and quickly diagnose a patient. For now, DETECTR was tested in a tube containing DNA from infected human cells, showing it could detect HPV16 with 100 percent accuracy, and HPV18 with 92 percent accuracy.


Called SHERLOCK, this system uses a variety of CRISPR enzymes, including Cas12a. Last year, Zhang’s team showed that SHERLOCK uses CRISPR-Cas13a to find the genetic sequence of Zika, dengue, and several other bacteria, as well as the sequences associated with a cancer mutation in a variety of human samples, such as saliva. Now, the team has improved the tool to be 100 times more sensitive and detect multiple viruses — such as Zika and dengue — in one sample simultaneously. It does this by combining different types of CRISPR enzymes, which are unleashed together to target distinct bits of DNA and RNA, another of the major biological molecules found in all forms of life. Some enzymes also work together to make the tool more sensitive.

If you read Doudna’s book, featured in the H+ “Key Books” section, you realise the enormous progress we made in the last 10 years in terms of DNA manipulation thanks to CRISPR, and yet you have a clear understanding that we are just scratching the surface of what is possible.

Sequence your genome for less than $1,000 and sell it via blockchain

From Human sequencing pioneer George Church wants to give you the power to sell your DNA on the blockchain | TechCrunch

MIT professor and godfather of the Human Genome Project George Church wants to put your genes on it.

His new startup Nebula Genomics plans to sequence your genome for less than $1,000 (the current going rate of whole genome sequencing) and then add your data to the blockchain through the purchase of a “Nebula Token.”

Church and his colleagues laid out in a recently released white paper that this will put the genomic power in the hands of the consumer, as opposed to companies like 23andMe and AncestryDNA, which own your genomic data after you take that spit tube test.

These companies sell that data in large swaths to pharmaceutical and research companies, often for millions of dollars. However, using the blockchain, consumers can choose to sell their own data directly.


Those buying up tokens and sequencing their DNA through Nebula don’t have to sell it for money, of course, and Nebula says they can still discover insights about their own genetics through the company app without sharing it elsewhere, if they desire.

However, all bought and sold data will be recorded on the blockchain, which is a technology allowing for the recording of all transactions using a key code known only to the person who holds the information.

Two thoughts:

  • If this idea generates even a tiny bit of money for each individual involved, it might unlock unprecedented access to genetic information for advanced engineering.
  • Our genome is the second last thing we’ve left to sell. The last one is our attention. But once they have our genome, our attention may come for free.

A biohacker injected himself with a DIY herpes treatment in front of a conference audience

From A biohacker injected himself with a DIY herpes treatment in front of a live audience – The Verge

Aaron Traywick, 28, who leads biotech firm Ascendance Biomedical, used an experimental herpes treatment that did not go through the typical route of clinical trials to test its safety.

Instead of being developed by research scientists in laboratories, it was created by a biohacker named Andreas Stuermer, who “holds a masters degree and is a bioentrepreneur and science lover,” according to a conference bio. This is typical of the Ascendance approach. The company believes that FDA regulations for developing treatments are too slow and that having biohackers do the research and experiment on themselves can speed up the process to everyone’s benefit. In the past, the company’s plans have included trying to reverse menopause, a method that is now actually in clinical trials.

From Biohackers Disregard FDA Warning on DIY Gene Therapy – MIT Technology Review

Experts say any gene therapy prepared by amateurs would probably not be potent enough to have much effect, but it could create risks such as an immune reaction to the foreign DNA. “I think warning people about this is the right thing,” says David Gortler, a drug safety expert with the consulting group Former FDA. “The bottom line is, this hasn’t been tested.”

The problem facing regulators is that interest in biohacking is spreading, and it’s increasingly easy for anyone to obtain DNA over the internet.

The last sentence is key. As in the tech industry, once you trigger bottom-up adoption the process is irreversible. And disruptive.

CRISPR might be employed to destroy entire species

From A Crack in Creation:

Ironically, CRISPR might also enable the opposite: forcible extinction of unwanted animals or pathogens. Yes, someday soon, CRISPR might be employed to destroy entire species—an application I never could have imagined when my lab first entered the fledgling field of bacterial adaptive immune systems just ten years ago. Some of the efforts in these and other areas of the natural world have tremendous potential for improving human health and well-being. Others are frivolous, whimsical, or even downright dangerous. And I have become increasingly aware of the need to understand the risks of gene editing, especially in light of its accelerating use. CRISPR gives us the power to radically and irreversibly alter the biosphere that we inhabit by providing a way to rewrite the very molecules of life any way we wish. At the moment, I don’t think there is nearly enough discussion of the possibilities it presents—for good, but also for ill.

We have a responsibility to consider the ramifications in advance and to engage in a global, public, and inclusive conversation about how to best harness gene editing in the natural world, before it’s too late.


If the first of these gene drives (for pigmentation) seems benign and the second (for malaria resistance) seems beneficial, consider a third example. Working independently of the California scientists, a British team of researchers—among them Austin Bud, the biologist who pioneered the gene drive concept—created highly transmissive CRISPR gene drives that spread genes for female sterility. Since the sterility trait was recessive, the genes would rapidly spread through the population, increasing in frequency until enough females acquired two copies, at which point the population would suddenly crash. Instead of eradicating malaria by genetically altering mosquitoes to prevent them from carrying the disease, this strategy presented a blunter instrument—one that would cull entire populations by hindering reproduction. If sustained in wild-mosquito populations, it could eventually lead to outright extermination of an entire mosquito species.


It’s been estimated that, had a fruit fly escaped the San Diego lab during the first gene drive experiments, it would have spread genes encoding CRISPR, along with yellow-body trait, to between 20 and 50 percent of all fruit flies worldwide.

The author of this book, Jennifer Doudna, is one of the first scientists that discovered the groundbreaking gene editing technique CRISPR-Cas9. The book is a fascinating narration of how CRISPR came to be, and it’s listed in the Key Books section of H+.

The book was finished in September 2016 (and published in June 2017), so the warning is quite recent.

You may also want to watch Doudna’s TED Talk about the bioethics of CRISPR: How CRISPR lets us edit our DNA.

“We have entered the age where the human genome is a real drug target” – CRISPR stopped mice from going deaf

From This gene therapy stopped mice from going deaf — and could save some humans’ hearing too – The Verge

Although people can lose their hearing for a variety of reasons — old age, as well as exposure to loud noises — genetics are behind a little less than half of all deafness cases, says study co-author David Liu, a professor of chemistry and chemical biology at Harvard, who also has affiliations with the Broad Institute and the Howard Hughes Medical Institute. The hearing-loss disease tackled in this study is caused by mutations in a gene called TMC1. These mutations cause the death of so-called hair cells in the inner ear, which convert mechanical vibrations like sound waves into nerve signals that the brain interprets as hearing. As a result, people start losing their hearing in their childhood or in the 20s, and can go completely deaf by their 50s and 60s.

To snip those mutant copies of the gene, Liu and his colleagues mixed CRISPR-Cas9 with a lipid droplet that allows the gene-editing tool to enter the hair cells and get to work. When the concoction was injected into one ear of newborn mice with the disease, the molecular scissors were able to precisely cut the deafness-causing copy of the gene while leaving the healthy copy alone, even if the two copies differ by just one base pair. The treatment allowed the hair cells to stay healthier and prevented the mice from going deaf.

After four weeks, the untreated ears could only pick up noises that were 80 decibels or louder, roughly as loud as a garbage disposal, Liu says. Instead, the injected ears could typically hear sounds in the 60 to 65 decibel range, which is the same as a quiet conversation. “If one can translate that 15 decibel improvement in hearing sensitivity in humans, it would actually make a potential difference in the quality of their hearing capability,” Liu tells The Verge.

DARPA has become the world’s largest funder of “gene drive” research

From US military agency invests $100m in genetic extinction technologies | Science | The Guardian

A US military agency is investing $100m in genetic extinction technologies that could wipe out malarial mosquitoes, invasive rodents or other species, emails released under freedom of information rules show.

The UN Convention on Biological Diversity (CBD) is debating whether to impose a moratorium on the gene research next year and several southern countries fear a possible military application.


Gene-drive research has been pioneered by an Imperial College London professor, Andrea Crisanti, who confirmed he has been hired by Darpa on a $2.5m contract to identify and disable such drives.

Human augmentation has, at least at the beginning, a very limited number of very specific use cases. The supersoldier certainly is the top one.

Defeating cancer costs $500,000 

From Genetic Programmers Are the Next Startup Millionaires – MIT Technology Review

Cell Design Labs, founded by University of California, San Francisco, synthetic biologist Wendell Lim, creates “programs” to install inside T cells, the killer cells of the immune system, giving them new abilities.

Known as “CAR-T,” the treatments are both revolutionary and hugely expensive. A single dose is priced at around $500,000 but often results in a cure. Gilead quickly paid $12 billion to acquire Kite Pharma, maker of one of those treatments.

The initial T cell treatments, however, work only with blood cancers.

From FDA Approves Groundbreaking Gene Therapy for Cancer – MIT Technology Review

The FDA calls the treatment, made by Novartis, the “first gene therapy” in the U.S. The therapy is designed to treat an often-lethal type of blood and bone marrow cancer that affects children and young adults. Known as a CAR-T therapy, the approach has shown remarkable results in patients. The one-time treatment will cost $475,000, but Novartis says there will be no charge if a patient doesn’t respond to the therapy within a month.

The therapy, which will be marketed as Kymriah, is a customized treatment that uses a patient’s own T cells, a type of immune cell. A patient’s T cells are extracted and cryogenically frozen so that they can be transported to Novartis’s manufacturing center in New Jersey. There, the cells are genetically altered to have a new gene that codes for a protein—called a chimeric antigen receptor, or CAR. This protein directs the T cells to target and kill leukemia cells with a specific antigen on their surface. The genetically modified cells are then infused back into the patient.

This is less than the $700,000 previously reported, but still a fortune.

In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation

From In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation: Cell

Current genome-editing systems generally rely on inducing DNA double-strand breaks (DSBs). This may limit their utility in clinical therapies, as unwanted mutations caused by DSBs can have deleterious effects. CRISPR/Cas9 system has recently been repurposed to enable target gene activation, allowing regulation of endogenous gene expression without creating DSBs. However, in vivo implementation of this gain-of-function system has proven difficult. Here, we report a robust system for in vivo activation of endogenous target genes through trans-epigenetic remodeling. The system relies on recruitment of Cas9 and transcriptional activation complexes to target loci by modified single guide RNAs. As proof-of-concept, we used this technology to treat mouse models of diabetes, muscular dystrophy, and acute kidney disease. Results demonstrate that CRISPR/Cas9-mediated target gene activation can be achieved in vivo, leading to measurable phenotypes and amelioration of disease symptoms. This establishes new avenues for developing targeted epigenetic therapies against human diseases.

CRISPR can be repurposed to enable target gene activation

From Adapted Crispr gene editing tool could treat incurable diseases, say scientists | The Guardian

The technique is an adapted version of the powerful gene editing tool called Crispr. While the original version of Crispr snips DNA in precise locations to delete faulty genes or over-write flaws in the genetic code, the modified form “turns up the volume” on selected genes.


In the new version a Crispr-style guide is still used, but instead of cutting the genome at the site of interest, the Cas9 enzyme latches onto it. The new package also includes a third element: a molecule that homes in on the Cas9 and switches on whatever gene it is attached to.


The team showed that mice, with a version of muscular dystophy, a fatal muscle wasting disorder, recovered muscle growth and strength. The illness is caused by a mutation in the gene that produces dystrophin, a protein found in muscle fibres. However, rather than trying to replace this gene with a healthy version, the team boosted the activity of a second gene that produces a protein called utrophin that is very similar to dystrophin and can compensate for its absence.

Of course, once you can activate genes at will, you can also boost a perfectly healthy human in areas where he/she is weak or inept.

Genetic engineering for skill enablement, that is.

Google open source tool DeepVariant achieves unprecedented accuracy in human genome sequencing

From Google Is Giving Away AI That Can Build Your Genome Sequence | Wired:

On Monday, Google released a tool called DeepVariant that uses deep learning—the machine learning technique that now dominates AI—to assemble full human genomes.

And now, engineers at Google Brain and Verily (Alphabet’s life sciences spin-off) have taught one to take raw sequencing data and line up the billions of As, Ts, Cs, and Gs that make you you.


Today, you can get your whole genome for just $1,000 (quite a steal compared to the $1.5 million it cost to sequence James Watson’s in 2008).

But the data produced by today’s machines still only produce incomplete, patchy, and glitch-riddled genomes. Errors can get introduced at each step of the process, and that makes it difficult for scientists to distinguish the natural mutations that make you you from random artifacts, especially in repetitive sections of a genome.

See, most modern sequencing technologies work by taking a sample of your DNA, chopping it up into millions of short snippets, and then using fluorescently-tagged nucleotides to produce reads—the list of As, Ts, Cs, and Gs that correspond to each snippet. Then those millions of reads have to be grouped into abutting sequences and aligned with a reference genome.

That’s the part that gives scientists so much trouble. Assembling those fragments into a usable approximation of the actual genome is still one of the biggest rate-limiting steps for genetics.


DeepVariant works by transforming the task of variant calling—figuring out which base pairs actually belong to you and not to an error or other processing artifact—into an image classification problem. It takes layers of data and turns them into channels, like the colors on your television set.

After the FDA contest they transitioned the model to TensorFlow, Google’s artificial intelligence engine, and continued tweaking its parameters by changing the three compressed data channels into seven raw data channels. That allowed them to reduce the error rate by a further 50 percent. In an independent analysis conducted this week by genomics computing platform, DNAnexus, DeepVariant vastly outperformed GATK, Freebayes, and Samtools, sometimes reducing errors by as much as 10-fold.

DeepVariant is now open source and available here:

Google competes with many other vendors on many fronts. But while his competitors are focused on battling for today’s market opportunities, Google is busy in a solitary race to control the battlefield of the future: the human body.

The human body is the ultimate data center.

Sangamo Therapeutics attempts to edit a gene inside the body for the first time

From AP Exclusive: US scientists try 1st gene editing in the body

.Scientists for the first time have tried editing a gene inside the body in a bold attempt to permanently change a person’s DNA to cure a disease

The experiment was done Monday in California on 44-year-old Brian Madeux. Through an IV, he received billions of copies of a corrective gene and a genetic tool to cut his DNA in a precise spot


Weekly IV doses of the missing enzyme can ease some symptoms, but cost $100,000 to $400,000 a year and don’t prevent brain damage.

Gene editing won’t fix damage he’s already suffered, but he hopes it will stop the need for weekly enzyme treatments.


The therapy has three parts: The new gene and two zinc finger proteins. DNA instructions for each part are placed in a virus that’s been altered to not cause infection but to ferry them into cells. Billions of copies of these are given through a vein.

They travel to the liver, where cells use the instructions to make the zinc fingers and prepare the corrective gene. The fingers cut the DNA, allowing the new gene to slip in. The new gene then directs the cell to make the enzyme the patient lacked.

Only 1 percent of liver cells would have to be corrected to successfully treat the disease, said Madeux’s physician and study leader, Dr. Paul Harmatz at the Oakland hospital.

Zinc finger nucleases is a different gene editing tool than CRISPR.

I originally wanted to wait the 3 months necessary to verify if this procedure worked, but this is history in the making, with enormous implications, and I want to have H+ to have it on the record.

I’ll update this article with the results of the therapy once they are disclosed.

It might be possible to treat diseases by giving aging tissues a signal to clean house

From Young Again: How One Cell Turns Back Time – The New York Times

None of us was made from scratch. Every human being develops from the fusion of two cells, an egg and a sperm, that are the descendants of other cells. The lineage of cells that joins one generation to the next — called the germline — is, in a sense, immortal.

Biologists have puzzled over the resilience of the germline for 130 years, but the phenomenon is still deeply mysterious.

Over time, a cell’s proteins become deformed and clump together. When cells divide, they pass that damage to their descendants. Over millions of years, the germline ought to become too devastated to produce healthy new life.


On Thursday in the journal Nature, Dr. Bohnert and Cynthia Kenyon, vice president for aging research at Calico, reported the discovery of one way in which the germline stays young.

Right before an egg is fertilized, it is swept clean of deformed proteins in a dramatic burst of housecleaning.


Combining these findings, the researchers worked out the chain of events by which the eggs rejuvenate themselves.

It begins with a chemical signal released by the sperm, which triggers drastic changes in the egg. The protein clumps within the egg “start to dance around,” said Dr. Bohnert.

The clumps come into contact with little bubbles called lysosomes, which extend fingerlike projections that pull the clumps inside. The sperm signal causes the lysosomes to become acidic. That change switches on the enzymes inside the lysosomes, allowing them to swiftly shred the clumps.

A new genetic engineering method based on CRISPR: Base Editing 

From CRISPR 2.0 Is Here, and It’s Way More Precise – MIT Technology Review

The human genome contains six billion DNA letters, or chemical bases known as A, C, G and T. These letters pair off—A with T and C with G—to form DNA’s double helix. Base editing, which uses a modified version of CRISPR, is able to change a single one of these letters at a time without making breaks to DNA’s structure.

That’s useful because sometimes just one base pair in a long strand of DNA gets swapped, deleted, or inserted—a phenomenon called a point mutation. Point mutations make up 32,000 of the 50,000 changes in the human genome known to be associated with diseases.

In the Nature study, researchers led by David Liu, a Harvard chemistry professor and member of the Broad Institute, were able to change an A into a G. Such a change would address about half the 32,000 known point mutations that cause disease.

To do it, they modified CRISPR so that it would target just a single base. The editing tool was able to rearrange the atoms in an A so that it instead resembled a G, tricking cells into fixing the other DNA strand to complete the switch. As a result, an A-T base pair became a G-C one. The technique essentially rewrites errors in the genetic code instead of cutting and replacing whole chunks of DNA.

The new method is also called ABE (adenine base editors).

From New Gene-Editing “Pencil” Erases Disease-Causing Errors – Scientific American

before ABE can be tried in human patients, Liu says, doctors would need to determine when to intervene in the course of a genetic disease. They would also have to figure out how to best deliver the gene editor to the relevant cells—and to prove the approach is safe and effective enough to make a difference for the patient.


The ABE gene-editing process is efficient, effectively editing the relevant spot in the genome an average of 53 percent of the time across 17 tested sites, Liu said. It caused undesired effects less than 0.1 percent of the time, he added. That success rate is comparable with what CRISPR can do when it is cutting genes.

It’s such an incredible moment to work (and invest) in life sciences.

Biohacker Attempts Editing His DNA With CRISPR

From This Guy Says He’s The First Person To Attempt Editing His DNA With CRISPR

the biohacker claims he’s the first person trying to modify his own genome with the groundbreaking gene-editing technology known as CRISPR. And he’s providing the world with the means to do it, too, by posting a “DIY Human CRISPR Guide” online and selling $20 DNA that promotes muscle growth.

But editing your DNA isn’t as simple as following step-by-step advice. Scientists say that injecting yourself with a gene for muscle growth, as Zayner’s done, won’t in fact pump up your arms. Zayner himself admits that his experiments over the last year haven’t visibly changed his body. There are safety risks, too, experts say: People could infect themselves, or induce an inflammatory reaction.

But to Zayner, whether or not the experiment actually works is besides the point. What he’s trying to demonstrate, Zayner told BuzzFeed News, is that cutting-edge biology tools like CRISPR should be available to people to do as they wish, and not be controlled by academics and pharmaceutical companies.

Another biohacker, Brian Hanley, popular for testing anti-age gene therapy on himself, commented Zayner’s kits with a post on the Institute for Ethics and Emerging Technologies:

Yes, there is a long history of scientists and physicians experimenting on themselves. 15 Nobel prizewinners did it. Hundreds of documented cases of prominent scientists doing it. I am sure there are thousands more such experiments by scientists that are not documented. There have been no documented deaths of scientists by self-experiment since 1928. But it is one thing for someone who really understands what they are doing to perform such experiments, or for qualified people to assist another qualified person. It is quite another thing for Joe programmer biohacker-hopeful to do that without really understanding it because some guy sold him a kit.

The point is not if it’s legit or not, effective or not, legal or not. The point is that there is a growing community of humans that is experimenting, tinkering, and taking risks with their bodies, trying to achieve things that the mainstream audience considers horrifying, impossible, out of reach. This community doesn’t have much credibility today, just like IT security hackers didn’t have much credibility in the early days of the Internet. Today, hacking communities are recruiting pools by top military organizations in the world, and hacking conferences are a prime stage for the biggest software and hardware vendors on the market.

Lost in a sea of pseudo-scientists, impostors, scammers, and amateur wannabe, there are a few serious, determined, fearless explorers of the human body. They won’t look credible until they will.

Cancer incidence increasing globally: The role of relaxed natural selection

From Cancer incidence increasing globally: The role of relaxed natural selection – You – 2017 – Evolutionary Applications

Cancer incidence increase has multiple aetiologies. Mutant alleles accumulation in populations may be one of them due to strong heritability of many cancers. The opportunity for the operation of natural selection has decreased in the past ~150 years because of reduction in mortality and fertility. Mutation-selection balance may have been disturbed in this process and genes providing background for some cancers may have been accumulating in human gene pools. Worldwide, based on the WHO statistics for 173 countries the index of the opportunity for selection is strongly inversely correlated with cancer incidence in peoples aged 0–49 years and in people of all ages. This relationship remains significant when gross domestic product per capita (GDP), life expectancy of older people (e50), obesity, physical inactivity, smoking and urbanization are kept statistically constant for fifteen (15) of twenty-seven (27) individual cancers incidence rates. Twelve (12) cancers which are not correlated with relaxed natural selection after considering the six potential confounders are largely attributable to external causes like viruses and toxins. Ratios of the average cancer incidence rates of the 10 countries with lowest opportunities for selection to the average cancer incidence rates of the 10 countries with highest opportunities for selection are 2.3 (all cancers at all ages), 2.4 (all cancers in 0–49 years age group), 5.7 (average ratios of strongly genetically based cancers) and 2.1 (average ratios of cancers with less genetic background).

Cancer treatment is a ‘double-edged sword’ by allowing survivors to pass on their tumour-causing genes

From Cancer treatment lets survivors pass on their tumour genes | Daily Mail Online

Because of the quality of our healthcare in western society, we have almost removed natural selection as the “janitor of the gene pool”.
‘Natural selection in the past had an ample opportunity to eliminate defective genes introduced by mutations.
He said: ‘However, natural selection has been significantly reduced in the past 100 to 150 years, and the direct consequence of this process is that nearly every individual born into a population can pass genes to the next generation, while some 150 years ago, only 50 per cent or less of individuals had this chance.
‘Unfortunately, the accumulation of genetic mutations over time and across multiple generations is like a delayed death sentence.
‘Allowing more people with cancer genes [to] survive may boost cancer gene accumulation. Patients who survive it will have a chance to pass this predisposition to the next generation.


Rather than just removing cancers, the researchers add patients should undergo genetic engineering that ‘turns off’ their tumour-causing genes.
Professor Henneberg added: ‘Assuming that the increasing genetic load underlies cancer incidence as one of the contributing factors, the only way to reduce it remains genetic engineering- repair of defective portions of the DNA or their blockage by methylation and similar approaches.
‘These techniques, though theoretically possible, are not yet practically available.
‘They will, however, need to be developed as they provide the only human-made alternative to the disappearing action of natural selection’.

Fascinating perspective and research. I think we are totally unequipped to understand the long-term implications of how we are changing the human body.

FDA approves First Gene Therapy That Fixes Hereditary Blindness

From The First Gene Therapy That Fixes Hereditary Blindness May Finally Get FDA Approval

Gene therapy typically uses an engineered virus to administer a patient with a faulty gene with a corrected version. Rather than simply responding to the symptoms of the condition in question, it attempts to make changes to the individual’s genetic make-up in order to solve the problem at its root.

Luxturna fixes a mutation in a gene known as RPE65, which is responsible for telling the body how to produce a protein that’s essential for normal eyesight. It introduces billions of engineered virus particles bearing a corrected version of the gene to the retinal cell, via a quick injection to the eyes.


It’s not an outright cure, and it doesn’t give recipients full 20/20 vision. There’s currently no data on how long its effects last, so there’s a chance that patients’ sight might begin to recede once again over time.

Cost is also a major factor in how accessible it is. Two of the treatment’s biggest competitors, Strimvelis and Kymriah, cost around $700,000 and $475,000 respectively.

It’s a lot of money to try something that is unlikely permanent, so at the moment this remains for very few privileged humans. But what an incredible step forward.

Development of an Intrinsic Skin Sensor for Blood Glucose Level with CRISPR-mediated Genome Editing in Epidermal Stem Cells

From Development of an Intrinsic Skin Sensor for Blood Glucose Level with CRISPR-mediated Genome Editing in Epidermal Stem Cells | bioRxiv

Biointegrated sensors can address various challenges in medicine by transmitting a wide variety of biological signals. A tempting possibility that has not been explored before is whether we can take advantage of genome editing technology to transform a small portion of endogenous tissue into an intrinsic and long-lasting sensor of physiological signals. The human skin and epidermal stem cells have several unique advantages, making them particularly suitable for genetic engineering and applications in vivo. In this report, we took advantage of a novel platform for manipulation and transplantation of epidermal stem cells, and presented the key evidence that genome-edited skin stem cells can be exploited for continuous monitoring of blood glucose level in vivo. Additionally, by advanced design of genome editing, we developed an autologous skin graft that can sense glucose level and deliver therapeutic proteins for diabetes treatment. Our results revealed the clinical potential for skin somatic gene therapy.

CRISPR used to genetically edit skin cells and turn them into a glucose detector

From Gene-Edited Skin Could Be Its Own Blood-Sugar Sensor – MIT Technology Review

To make their biological invention, Wu and team first collected from mice some of the stem cells whose job it is to make new skin. Next, they used the gene-editing technique CRISPR to create their built-in glucose detector. That involved adding a gene from E. coli bacteria whose product is a protein that sticks to sugar molecules.

Next, they added DNA that produces two fluorescent molecules. That way, when the E. coli protein sticks to sugar and changes shape, it moves the fluorescent molecules closer or further apart—generating a signal that Wu’s team could see using a microscope.

All that was done in a lab dish—so next the team tested whether the glucose-sensing cells could be incorporated into a mouse’s body by grafting the engineered skin patches onto their backs. When mice who were left hungry were suddenly given a big dose of sugar, Wu says, the cells reacted within 30 seconds. Measuring glucose this way was just as accurate as a blood test, which they also tried.

RNA targeting with CRISPR–Cas13

From RNA targeting with CRISPR–Cas13 : Nature

RNA has important and diverse roles in biology, but molecular tools to manipulate and measure it are limited. For example, RNA interference can efficiently knockdown RNAs, but it is prone to off-target effects, and visualizing RNAs typically relies on the introduction of exogenous tags. Here we demonstrate that the class 2 type VI RNA-guided RNA-targeting CRISPR–Cas effector Cas13a (previously known as C2c2) can be engineered for mammalian cell RNA knockdown and binding.

After initial screening of 15 orthologues, we identified Cas13a from Leptotrichia wadei (LwaCas13a) as the most effective in an interference assay in Escherichia coli. LwaCas13a can be heterologously expressed in mammalian and plant cells for targeted knockdown of either reporter or endogenous transcripts with comparable levels of knockdown as RNA interference and improved specificity. Catalytically inactive LwaCas13a maintains targeted RNA binding activity, which we leveraged for programmable tracking of transcripts in live cells.

Our results establish CRISPR–Cas13a as a flexible platform for studying RNA in mammalian cells and therapeutic development.

Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9

From Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9: Cell

Microsatellite repeat expansions in DNA produce pathogenic RNA species that cause dominantly inherited diseases such as myotonic dystrophy type 1 and 2 (DM1/2), Huntington’s disease, and C9orf72-linked amyotrophic lateral sclerosis (C9-ALS). Means to target these repetitive RNAs are required for diagnostic and therapeutic purposes. Here, we describe the development of a programmable CRISPR system capable of specifically visualizing and eliminating these toxic RNAs. We observe specific targeting and efficient elimination of microsatellite repeat expansion RNAs both when exogenously expressed and in patient cells. Importantly, RNA-targeting Cas9 (RCas9) reverses hallmark features of disease including elimination of RNA foci among all conditions studied (DM1, DM2, C9-ALS, polyglutamine diseases), reduction of polyglutamine protein products, relocalization of repeat-bound proteins to resemble healthy controls, and efficient reversal of DM1-associated splicing abnormalities in patient myotubes. Finally, we report a truncated RCas9 system compatible with adeno-associated viral packaging. This effort highlights the potential of RCas9 for human therapeutics.

Locana uses CRISPR to target RNA, not DNA, and address Huntington’s disease, ALS and myotonic dystrophy

From Arming Bodies with CRISPR to Fight Huntington’s Disease and ALS – MIT Technology Review

Normally, CRISPR uses a slicing protein called Cas9 that recognizes and chops up the desired DNA, eliminating a mutated gene. Yeo and his team modified Cas9 to leave DNA alone and instead bind to and cut problematic RNA.

When tested in the lab, Yeo’s CRISPR tool obliterated 95 percent or more of these RNA knots in cells harboring Huntington’s disease and a type of ALS.

The researchers also tested the approach on a form of inherited muscular dystrophy, called myotonic dystrophy. They were able to eliminate 95 percent of faulty RNAs in muscle cells taken from patients. After they applied CRISPR, the once-diseased cells resembled healthy ones. Yeo thinks more than 20 genetic diseases that are caused by toxic RNA repeats could potentially be treated this way.

Knocking down these RNAs is only temporary, though. RNA constantly regenerates, so its level in cells eventually rebounds back to normal after a few days to a week.


So Yeo is designing a virus capsule to carry the CRISPR machinery to the right cells. These viral delivery shuttles would allow the Cas protein to stick around in a person’s cells longer—ideally for years, turning Cas into a mini-arsenal to keep unruly RNA at bay.

Genome editing reveals a role for OCT4 in human embryogenesis

From Genome editing reveals a role for OCT4 in human embryogenesis : Nature

Despite their fundamental biological and clinical importance, the molecular mechanisms that regulate the first cell fate decisions in the human embryo are not well understood. Here we use CRISPR–Cas9-mediated genome editing to investigate the function of the pluripotency transcription factor OCT4 during human embryogenesis. We identified an efficient OCT4-targeting guide RNA using an inducible human embryonic stem cell-based system and microinjection of mouse zygotes. Using these refined methods, we efficiently and specifically targeted the gene encoding OCT4 (POU5F1) in diploid human zygotes and found that blastocyst development was compromised. Transcriptomics analysis revealed that, in POU5F1-null cells, gene expression was downregulated not only for extra-embryonic trophectoderm genes, such as CDX2, but also for regulators of the pluripotent epiblast, including NANOG. By contrast, Pou5f1-null mouse embryos maintained the expression of orthologous genes, and blastocyst development was established, but maintenance was compromised. We conclude that CRISPR–Cas9-mediated genome editing is a powerful method for investigating gene function in the context of human development.

CRISPR has revealed a clue in how human embryos begin to develop

From CRISPR breakthrough could drop miscarriage rates | TechCrunch

CRISPR Cas9 can modify or snip out genetic defects thought to contribute to miscarriage, but until now it wasn’t clear why some embryos continued to form into a fetus and others did not.

British scientists conducting the study found that a certain human genetic marker called OTC4 played an important role in the formation and development in the early stages of embryonic development. The scientists used CRISPR Cas9 to knock out this important gene in days-old human embryos and found that without it, these embryos ceased to attach or grow properly.

The findings could not only help us better understand why some women suffer more miscarriages than others, but it could also potentially greatly increase the rate of successful in vitro fertilization (IVF) procedures.

People could be identified using their DNA to predict their physical traits

From Geneticists pan paper that claims to predict a person’s face from their DNA : Nature

Venter and colleagues at his company Human Longevity, Inc. (HLI), based in San Diego, California, sequenced the whole genomes of 1,061 people of varying ages and ethnic backgrounds. Using the genetic data, along with high-quality 3D photographs of the participants’ faces, the researchers used an artificial intelligence approach to find small differences in DNA sequences, called SNPs, associated with facial features such as cheekbone height. The team also searched for SNPs that correlated with factors including a person’s height, weight, age, vocal characteristics and skin colour.

The approach correctly identified an individual out of a group of ten people randomly selected from HLI’s database 74% of the time. The findings, according to the paper, suggest that law-enforcement agencies, scientists and others who handle human genomes should protect the data carefully to prevent people from being identified by their DNA alone.

The scientific community, including a co-author (who works for Apple), suggests that the paper misrepresented the data.

The point is that we are going in that direction and the progress is remarkable. The scientist reviewing the paper for Nature said:

HLI’s actual data are sound, and he is impressed with the group’s novel method of determining age by sequencing the ends of chromosomes, which shorten over time.

U.S. attitudes on human genome editing

From U.S. attitudes on human genome editing | Science

The emergence of CRISPR-Cas9 gene editing has given new urgency to calls from social scientists, bench scientists, and scientific associations for broad public dialogue about human genome editing and its applications. Most recently, these calls were formalized in a consensus report on the science, ethics, and governance of human genome editing released by the U.S. National Academy of Sciences (NAS) and the National Academy of Medicine (NAM) that argued for public engagement to be incorporated into the policy-making process for human genome editing (1). So, where does the public stand on the issue of human genome editing? And how do those attitudes translate into the desire for more public input on human genome editing as new applications emerge in the policy arena?

How does the public feel about editing human DNA?

From Two-thirds of Americans approve of editing human DNA to treat disease – The Verge

First of all, gene editing can mean a lot of different things: you can edit the human genome for therapeutic purposes, to treat disease, for instance; or potentially to “enhance” human abilities, such as intelligence. And those changes can be made so that they’re passed on to future generations (so-called germline editing) or so that they affect only the individual whose cells are being edited (somatic editing).

Scheufele wanted to survey the public on gene editing in all its nuances, because people may have very different opinions on whether embryos are edited to cure a crippling disease or to boost a kid’s intelligence. (None of these things have been accomplished yet; the research is still in its infancy.) And one of his findings took Scheufele by surprise: he expected people to draw a line when it comes to all kinds of germline editing. After all, edits that can be passed on to future generations can change the human gene pool forever — and we don’t really know what the consequences might be. But he found that people really only drew a line when editing, especially germline editing, was for “enhancement” rather than treating disease.

Correction of a pathogenic gene mutation in human embryos

From Correction of a pathogenic gene mutation in human embryos – Nature

Genome editing has potential for the targeted correction of germline mutations. Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR–Cas9-based targeting accuracy and high homology-directed repair efficiency by activating an endogenous, germline-specific DNA repair response.

Induced double-strand breaks (DSBs) at the mutant paternal allele were predominantly repaired using the homologous wild-type maternal gene instead of a synthetic DNA template. By modulating the cell cycle stage at which the DSB was induced, we were able to avoid mosaicism in cleaving embryos and achieve a high yield of homozygous embryos carrying the wild-type MYBPC3 gene without evidence of off-target mutations.

First Human Embryos Edited with CRISPR in US

From First Human Embryos Edited in U.S. – MIT Technology Review

The first known attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon, MIT Technology Review has learned. The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved changing the DNA of a large number of one-cell embryos with the gene-editing technique CRISPR

To date, three previous reports of editing human embryos were all published by scientists in China.

Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.

One week later, additional details emerge.

From US scientists have corrected a genetic heart mutation in embryos using CRISPR | TechCrunch

Shoukhrat Mitalipov and his colleagues from Oregon Health and Science University have successfully used the CRISPR Cas9 gene editing technology to wipe out a genetically inherited heart mutation in embryos.

Mitalipov and his colleagues were able to avoid the previous mistakes made by the Chinese scientists by injecting the Cas9 enzyme (which acts as a sort of scissors for DNA fragments) into the sperm and eggs at the same time.

What an incredible moment in history to witness.

Amazon has a secret unit called 1492 focused on health tech

From Amazon 1492: secret health tech project

The stealth team, which is headquartered in Seattle, is focused on both hardware and software projects, according to two people familiar. Amazon has become increasingly interested in exploring new business in healthcare. For example, Amazon has another unit exploring selling pharmaceuticals, CNBC reported in May.

The new team is currently looking at opportunities that involve pushing and pulling data from legacy electronic medical record systems. If successful, Amazon could make that information available to consumers and their doctors.
1492 Conquer of Paradise.

I wouldn’t be surprised if long-term goal of this unit would be, just like for Google’s Verily, genetic engineering and anti-aging medical research.

New protein AcrIIA4 increases CRISPR-CAS9 precision

From This DNA-mimicking protein can make gene editing more precise and safe – The Verge

Even though gene-editing tools like CRISPR-Cas9 are very precise, they sometimes snip pieces of DNA they weren’t programmed to cut. These off-target cuts can be dangerous, and scientists have been trying to find ways to prevent them.

The researchers found that the protein AcrIIA4 mimics DNA so that it can bind to the Cas9 enzyme, blocking it from attaching to actual DNA and cutting it.

Finally, the researchers added AcrIIA4 a few hours after adding the Cas9; that prevented CRISPR from cutting DNA at the wrong sites, while still allowing time for cutting at the right sites.

New Study Demonstrates Potential for AI and Whole Genome Sequencing to Scale Access to Precision Medicine

From IBM News room – 2017-07-11 Study by New York Genome Center and IBM Demonstrates Potential for AI and Whole Genome Sequencing to Scale Access to Precision Medicine – United States

researchers at the New York Genome Center (NYGC), The Rockefeller University and other NYGC member institutions, and IBM (NYSE: IBM) bhave illustrated the potential of IBM Watson for Genomics to analyze complex genomic data from state-of-the-art DNA sequencing of whole genomes. The study compared multiple techniques – or assays – used to analyze genomic data from a glioblastoma patient’s tumor cells and normal healthy cells.

The proof of concept study used a beta version of Watson for Genomics technology to help interpret whole genome sequencing (WGS) data for one patient. In the study, Watson was able to provide a report of potential clinically actionable insights within 10 minutes, compared to 160 hours of human analysis and curation required to arrive at similar conclusions for this patient.

Comparing sequencing assays and human-machine analyses in actionable genomics for glioblastoma

From Comparing sequencing assays and human-machine analyses in actionable genomics for glioblastoma

Objective: To analyze a glioblastoma tumor specimen with 3 different platforms and compare potentially actionable calls from each.

Methods: Tumor DNA was analyzed by a commercial targeted panel. In addition, tumor-normal DNA was analyzed by whole-genome sequencing (WGS) and tumor RNA was analyzed by RNA sequencing (RNA-seq). The WGS and RNA-seq data were analyzed by a team of bioinformaticians and cancer oncologists, and separately by IBM Watson Genomic Analytics (WGA), an automated system for prioritizing somatic variants and identifying drugs.

Results: More variants were identified by WGS/RNA analysis than by targeted panels. WGA completed a comparable analysis in a fraction of the time required by the human analysts.

Conclusions: The development of an effective human-machine interface in the analysis of deep cancer genomic datasets may provide potentially clinically actionable calls for individual patients in a more timely and efficient manner than currently possible.

Would you start saving money for college tuition, or for printing the genome of your offspring?

From Stanford’s Final Exams Pose Question About the Ethics of Genetic Engineering | Futurism

When bioengineering students sit down to take their final exams for Stanford University, they are faced with a moral dilemma, as well as a series of grueling technical questions that are designed to sort the intellectual wheat from the less competent chaff: “If you and your future partner are planning to have kids, would you start saving money for college tuition, or for printing the genome of your offspring?”

The question is a follow up to “At what point will the cost of printing DNA to create a human equal the cost of teaching a student in Stanford?”

I’d love to see the breakdown by gender, ethnicity, etc. and how the answers evolve year over year.

The Slippery Slope Argument in the Ethical Debate on Genetic Engineering of Humans

From The Slippery Slope Argument in the Ethical Debate on Genetic Engineering of Humans | SpringerLink

This article applies tools from argumentation theory to slippery slope arguments used in current ethical debates on genetic engineering. Among the tools used are argumentation schemes, value-based argumentation, critical questions, and burden of proof. It is argued that so-called drivers such as social acceptance and rapid technological development are also important factors that need to be taken into account alongside the argumentation scheme. It is shown that the slippery slope argument is basically a reasonable (but defeasible) form of argument, but is often flawed when used in ethical debates because of failures to meet the requirements of its scheme.

Genetic Engineering and Human Mental Ecology: Interlocking Effects and Educational Considerations

From Genetic Engineering and Human Mental Ecology: Interlocking Effects and Educational Considerations | SpringerLink

This paper describes some likely semiotic consequences of genetic engineering on what Gregory Bateson has called “the mental ecology” (1979) of future humans, consequences that are less often raised in discussions surrounding the safety of GMOs (genetically modified organisms). The effects are as follows: an increased 1) habituation to the presence of GMOs in the environment, 2) normalization of empirically false assumptions grounding genetic reductionism, 3) acceptance that humans are capable and entitled to decide what constitutes an evolutionary improvement for a species, 4) perception that the main source of creativity and problem solving in the biosphere is anthropogenic. Though there are some tensions between them, these effects tend to produce self-validating webs of ideas, actions, and environments, which may reinforce destructive habits of thought. Humans are unlikely to safely develop genetic technologies without confronting these escalating processes directly. Intervening in this mental ecology presents distinct challenges for educators, as will be discussed.