Human embryos edited to stop disease


Embryo

Scientists have, for the first time, successfully freed embryos of a piece of faulty DNA that causes deadly heart disease to run in families.

It potentially opens the door to preventing 10,000 disorders that are passed down the generations.

The US and South Korean team allowed the embryos to develop for five days before stopping the experiment.

The study hints at the future of medicine, but also provokes deep questions about what is morally right.

Science is going through a golden age in editing DNA thanks to a new technology called Crispr, named breakthrough of the year in just 2015.

Its applications in medicine are vast and include the idea of wiping out genetic faults that cause diseases from cystic fibrosis to breast cancer.

Heart stopper

US teams at Oregon Health and Science University and the Salk Institute along with the Institute for Basic Science in South Korea focused on hypertrophic cardiomyopathy.

The disorder is common, affecting one in every 500 people, and can lead to the heart suddenly stopping beating.

It is caused by an error in a single gene (an instruction in the DNA), and anyone carrying it has a 50-50 chance of passing it on to their children.

In the study, described in the journal Nature, the genetic repair happened during conception.

Sperm from a man with hypertrophic cardiomyopathy was injected into healthy donated eggs alongside Crispr technology to correct the defect.

It did not work all the time, but 72% of embryos were free from disease-causing mutations.

Eternal benefit

Dr Shoukhrat Mitalipov, a key figure in the research team, said: “Every generation on would carry this repair because we’ve removed the disease-causing gene variant from that family’s lineage.

“By using this technique, it’s possible to reduce the burden of this heritable disease on the family and eventually the human population.”

There have been multiple attempts before, including, in 2015, teams in China using Crispr-technology to correct defects that lead to blood disorders.

But they could not correct every cell, so the embryo was a “mosaic” of healthy and diseased cells.

Their approach also led to other parts of the genetic code becoming mutated.

Those technical obstacles have been overcome in the latest research.

However, this is not about to become routine practice.

The biggest question is one of safety, and that can be answered only by far more extensive research.

There are also questions about when it would be worth doing – embryos can already be screened for disease through pre-implantation genetic diagnosis.

However, there are about 10,000 genetic disorders that are caused by a single mutation and could, in theory, be repaired with the same technology.

Prof Robin Lovell-Badge, from the Francis Crick Institute, told the BBC: “A method of being able to avoid having affected children passing on the affected gene could be really very important for those families.

“In terms of when, definitely not yet. It’s going to be quite a while before we know that it’s going to be safe.”

Nicole Mowbray

Nicole Mowbray lives with hypertrophic cardiomyopathy and has a defibrillator implanted in her chest in case her heart stops.

But she is unsure whether she would ever consider gene editing: “I wouldn’t want to pass on something that caused my child to have a limited or painful life.

“That does come to the front of my mind when I think about having children.

“But I wouldn’t want to create the ‘perfect’ child, I feel like my condition makes me, me.”

Ethical?

Darren Griffin, a professor of genetics at the University of Kent, said: “Perhaps the biggest question, and probably the one that will be debated the most, is whether we should be physically altering the genes of an IVF embryo at all.

“This is not a straightforward question… equally, the debate on how morally acceptable it is not to act when we have the technology to prevent these life-threatening diseases must also come into play.”

The study has already been condemned by Dr David King, from the campaign group Human Genetics Alert, which described the research as “irresponsible” and a “race for first genetically modified baby”.

Dr Yalda Jamshidi, a reader in genomic medicine at St George’s University of London, said: “The study is the first to show successful and efficient correction of a disease-causing mutation in early stage human embryos with gene editing.

“Whilst we are just beginning to understand the complexity of genetic disease, gene-editing will likely become acceptable when its potential benefits, both to individuals and to the broader society, exceeds its risks.”

The method does not currently fuel concerns about the extreme end of “designer babies” engineered to have new advantageous traits.

The way Crispr is designed should lead to a new piece of engineered DNA being inserted into the genetic code.

However, in a complete surprise to the researchers, this did not happen.

Instead, Crispr damaged the mutated gene in the father’s sperm, leading to a healthy version being copied over from the mother’s egg.

This means the technology, for now, works only when there is a healthy version from one of the parents.

Prof Lovell-Badge added: “The possibility of producing designer babies, which is unjustified in any case, is now even further away.”

Making the Makers


Mathematical optimization for self-production may explain mysterious features of the ribosome.
Rendering of the structure of the eukaryotic ribosome. Ribosomal RNA is represented as a grey tube. Proteins are shown in blue, orange and red. Image: Wikimedia Commons

Every living cell, whether a single bacterium or a human neuron, is a biological system as dynamic and complex as any city. Contained within cells are walls, highways, power plants, libraries, recycling centers and much more, all working together in unison to ensure the continuation of life.

The vast majority of these myriad structures are made of and made by proteins, and those proteins are made by one uniquely important molecular machine, the ribosome.

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In a new study published in Nature on July 20, a team led by Johan Paulsson, professor of systems biology at Harvard Medical School, now reveals the likely origin of several previously mysterious characteristics of the ribosome.

They mathematically demonstrated that ribosomes are precisely structured to produce additional ribosomes as quickly as possible, in order to support efficient cell growth and division.

The study’s theoretical predictions accurately reflect observed large-scale features—revealing why are ribosomes made of an unusually large number of small, uniformly sized proteins and a few strands of RNA that vary greatly in size—and provide perspective on the evolution of an exceptional molecular machine.

“The ribosome is one of the most important molecular complexes in all of life, and it’s been studied across scientific disciplines for decades,” Paulsson said.

“I was always puzzled by the fact that it seemed like we could explain its finer details, but ribosomes have these bizarre features that have not often been addressed, or if so in an unsatisfying way,” he said.

Mysterious features

Atomic structure of a ribosome subunit from an archaea, a type of microorganism. Proteins are shown in blue and RNA chains in orange and yellow. Animation: Wikimedia Commons/David GoodsellAtomic structure of a ribosome subunit from an archaea, a type of microorganism. Proteins are shown in blue and RNA chains in orange and yellow. Animation: Wikimedia Commons/David GoodsellAlthough scientists have unlocked how ribosomes turn genetic information into proteins at atomic resolution, revealing a molecular machine finely tuned for accuracy, speed and control, it hasn’t been clear what advantages lay in its several large-scale features.

Ribosomes are composed of a puzzlingly large number of different structural proteins—anywhere from 55 to 80, depending on organism type. These proteins are not just more numerous than expected, they are unusually short and uniform in length. Ribosomes are also composed of two to three strands of RNA, which account for up to 70 percent of the total mass of the ribosome.

“Without understanding why collective features exist, it is a bit like looking at a forest and understanding how chloroplasts and photosynthesis work, and not being able to explain why there are trees instead of grass,” Paulsson said.

So Paulsson and his collaborators Shlomi Reuveni, an HMS postdoctoral fellow, and Måns Ehrenberg of Uppsala University in Sweden, decided to look at the ribosome in a different light.

“Our breakthrough came by zooming out from the atomic and looking at the ribosome from a different perspective,” Reuveni said. “We didn’t think of the ribosome as a machine that produces proteins, but rather as the product of the protein production process.”

Forest for the trees

For a cell to divide, it must have two full sets of ribosomes to make all the proteins that the daughter cells will need. The speed at which ribosomes can make themselves, therefore, places a hard limit on how fast cell division occurs. Paulsson and his colleagues devised theoretical mathematical models for what the ribosome’s features should look like if speed was the primary selective pressure that drove its evolution.

The team calculated that distributing the task of making a new ribosome among many ribosomes—each making a small piece of the final product—can increase the rate of production by as much as 30 percent, since each new ribosome helps make more ribosomes as soon as they are created, accelerating the process.

This represents an enormous advantage for cells that need to divide quickly, such as bacteria. However, the protein production process takes time to initiate, and this overhead cost limits the number of proteins that a ribosome can be made of, according to the math.

The team’s models predicted that, for maximum self-production efficacy, a ribosome should be made of between 40 and 80 proteins. Each of these proteins should be around three times smaller than an average cellular protein, and they should all be roughly similar in size.

“We started with the theory, and certain features emerged. When we looked at data to compare with what our math predicted, we found in most cases that they matched what is seen in nature” – Reuveni

It turns out that the researchers’ theory, developed completely independently of the laboratory, accurately reflects the observed protein composition of the ribosome.

“An analogy for our findings would be to think of ribosomes not as a group of carpenters who merely build a lot of houses, but as carpenters who also build other carpenters,” Paulsson said. “There is then an incentive to divide the job into many small pieces that can be done in parallel to more quickly assemble another complete carpenter to help in the process.”

Theory and reality

Paulsson and his colleagues also examined ribosomal RNA, which act as a structural component and carry out the ribosome’s enzymatic activity of linking amino acids together into proteins.

Their analysis showed that, the more RNA a ribosome is made of, the more rapidly it can be produced. This is because cells can make RNA orders of magnitude faster than protein. Thus, while RNA enzymes are thought to be less efficient than protein enzymes, ribosomes have enormous pressure to use as much RNA as possible to maximize the rate at which more ribosomes can be made.

“Any place the ribosome can get away with using RNA, it should use it because self-production speed can essentially be doubled or tripled,” Paulsson said. “Even if RNA were inferior compared to protein for enzymatic function, there is still a great advantage to using RNA if a cell is trying to produce ribosomes as fast as possible.”

This observation was predicted to hold primarily for self-producing ribosomes, according to the team. Most other structures in the cell do not self-produce and can sacrifice production speed for the stability and efficacy provided by using protein instead of RNA.

Taken together, the team’s theory accurately predicts large-scale features of the ribosome that are seen across domains of life. It explains why the fastest growing organisms, such as bacteria, have the shortest ribosomal proteins and the greatest amounts of RNA. At the opposite end of the spectrum are mitochondria—the power plants of eukaryotic cells, which are thought to have once been bacteria that entered a permanent symbiotic state. Mitochondria have their own ribosomes that do not produce themselves. Without this pressure, mitochondrial ribosomes are indeed made of larger proteins and far less RNA than cellular ribosomes.

“When we started this project, we didn’t have a long list of features that we tried to explain through theory,” Reuveni said. “We started with the theory, and certain features emerged. When we looked at data to compare with what our math predicted, we found in most cases that they matched what is seen in nature.”

Rather than being mere relics of an evolutionary past, the unusual features of ribosomes thus seem to reflect an additional layer of functional optimization acting on collective properties of its parts, the team writes.

“While this study is basic science, we are addressing something that is shared by all life,” Paulsson said. “It is important that we understand where the constraints on structure and function come from, because like much of basic science, it is unpredictable what the consequences of new knowledge can unlock in the future.”

US Launches 10 Year Program to Track DNA in 1 Million People


President Obama’s Precision Medicine Initiative (PMI) has set forth on its ambitious journey, mapping the DNA of one million volunteers. The potential upside is massive, unlocking key genetic information that could finally turn the battle against many health disorders with more effective, targeted treatments for diseases like cancer and diabetes. The initiative could last more than a decade and cost over a billion dollars. Participants will share their genetic data, biological samples, lifestyle and diet information. Also under consideration are mobile health devices and wearables that will collect data about the participant’s health and environmental conditions between doctors’ visits.

The power of the initiative will ultimately be the creation of a standardized, central and shared repository of the one million volunteers. But exactly what data is collected, and how it will be transmitted and stored in the U.S.’s incompatible medical health systems has not yet been determined.

A “dream team” has been appointed by the President, including Andrew Conrad, Google’s “medicine man” and head of Google X’s Life Sciences team. Sue Siegel, CEO of GE Ventures and Healthymagination, will also join the team. Tony Coles, also on the team, who is the CEO of Yumanity Therapeutics insists, “We count on the government, and academia, to really help us understand the basic biology of disease – they’re far better suited to unlock the mysteries of the human body than industry. Once they help us understand the basic biology of disease, we can very specifically target our resources, and use those insights to develop new therapies,” he said.

The private industry has collected similar patient data for years. But they have not been willing to share the data outside exclusive partnerships — some say selfishly. The data represents intellectual property used to create new revenue generating products; while the industry will point to the protection of patient’s data. Google’s 23andMe has already accumulated over 850,000 genotyped customers and just last month launched into drug research and discovery, using these same samples where customers have granted their permission; over 80% have done so.

Juggernauts such as Genentech, Illumina and Celera, have also been documenting citizen DNA long before the PMI. These companies already have the intellectual property, talent and expertise in precision medicine research. In fact, Illumina has been contracted to provide all of the sequencing, for the U.K.’s 100,000 Genomes Project.

The PMI is an extremely worthy goal; one that someday I predict, will be viewed as the science and medical world’s equivalent to NASA’s Apollo program. But — only when it makes it off the launch pad. Science history repeatedly has shown government should not go it alone.  The Human Genome Project, Space X, the World Wide Web and most similarly the U.K.’s 100,000 Genomes Project — all propelled forward only when the public and private sectors have partnered. Ultimately, it will take both to deliver a huge payload of health benefits to U.S. citizens.

CRISPR, Life Altering Genetic Innovation


The scientific community is in the midst of a gold rush in new technological applications all made possible by the CRISPR/Cas9 system. CRISPR, short for “clustered regularly interspaced palindromic repeats” is quite possibly the biggest innovation in biological science since PCR was developed over three decades ago. This is literally life altering genetic innovation.

CRISPR_technology.png

Scientists have been modifying genomes for years, so what’s the big deal behind this new technology?

In the past, prior to 2010, in order to modify the genome of a mouse, researchers would transfer embryonic stem cells into a mouse embryo containing the genetic mutation of choice. It would then take three generations to see the desired mutation and actually start utilizing the mutation for research purposes. This resulted in large amounts of time and money spent on breeding two unnecessary generations of mice without the guarantee of success. If a researcher wished to modify five genes of interest, this process would be repeated, you guessed it, five more times.

Taking this into account, CRISPR only needs one generation. This system is precise, efficient, and flexible, allowing for multiple mutations to be made all at once. Its efficacy has been proven time and time again in mice, monkeys, and recently in non-viable human embryos by a group of researchers in China, which proves its potential to treat ANY genetic disease.

As applications of this system are developed, many billion-dollar opportunities will arise. With this much money at stake along with world changing potential, rights to the invention are sure to create a heated patent battle at the USPTO, begging the question; who owns the technology anyways?

Professor Jennifer Doudna of UC Berkeley and Emmanuelle Charpentier from Umea University in Sweden filed on March 15, 2013 – one day before the first-to-file rule took effect – and claimed a priority date of May 25, 2012. On the other hand, Feng Zhang of the broad institute of MIT and Harvard in Cambridge, Massachusetts filed on October 15, 2013 under the accelerated examination program. The Broad Institute received patent No. 8,697,359 in April of 2014 claiming priority to a provisional application filed in December 2012.

As the Broad Institute continued to file applications for the technology, Doudna filed a Suggestion of Interference claiming that the Broad Institute Patents interfered with Doudna’s previous application. Pre AIA gives right to who created the invention first, unlike the first-to-file rules of today. An interference procedure is underway with oral arguments set for November 2016.

At stake are the rights to exclusively make, use, license, and sell the invention. The CRISPR/Cas9 system has the ability to completely alter how we treat genetic diseases, and may lead to the actualization of ‘designer babies’ – babies born with their traits hand picked by the parents. The discovery of a lifetime is up for grabs and it will be interesting to see who emerges with rights to the technology. Each party has issued liscences to large biotech companies ready to use the technology in grand-scale implication, however these projects have been delayed, pending the USPTO decision of this patent battle.

Gene therapy technique may help prevent cancer metastasis. 


The spread of malignant cells around the body, known as metastasis, is the leading cause of mortality in women with breast cancer.

Now, a new gene therapy technique being developed by researchers at MIT is showing promise as a way to prevent breast cancer tumors from metastasizing.

The treatment, described in a paper published today in the journal Nature Communications, uses microRNAs—small noncoding RNA molecules that regulate gene expression—to control metastasis.

The therapy could be used alongside chemotherapy to treat early-stage breast cancer tumors before they spread, according to Natalie Artzi, a principal research scientist at MIT’s Institute for Medical Engineering and Science (IMES) and an assistant professor of medicine at Brigham and Women’s Hospital, who led the research in collaboration with Noam Shomron, an assistant professor on the faculty of medicine at Tel-Aviv University in Israel.

“The idea is that if the cancer is diagnosed early enough, then in addition to treating the primary tumor [with chemotherapy], one could also treat with specific microRNAs, in order to prevent the spread of cancer cells that cause metastasis,” Artzi says.

The regulation of gene expression by microRNAs is known to be important in preventing the spread of cancer cells. Recent studies by the Shomron team in Tel-Aviv have shown that disruption of this regulation, for example by genetic variants known as single nucleotide polymorphisms (SNPs), can have a significant impact on gene expression levels and lead to an increase in the risk of cancer.

To identify the specific microRNAs that play a role in breast cancer progression and could therefore potentially be used to suppress metastasis, the research teams first carried out an extensive bioinformatics analysis.

They compared three datasets: one for known SNPs; a second for sites at which microRNAs bind to the genome; and a third for breast cancer-related genes known to be associated with the movement of cells.

This analysis revealed a variant, or SNP, known as rs1071738, which influences metastasis. They found that this SNP disrupts binding of two microRNAs, miR-96 and miR-182. This disruption in turn prevents the two microRNAs from controlling the expression of a protein called Palladin.

Previous research has shown that Palladin plays a key role in the migration of breast cancer cells, and their subsequent invasion of otherwise healthy organs.

When the researchers carried out in vitro experiments in cells, they found that applying miR-96 and miR-182 decreased the expression of Palladin levels, in turn reducing the ability of breast cancer cells to migrate and invade other tissue.

“Previous research had discussed the role of Palladin in controlling migration and invasion (of cancer cells), but no one had tried to use microRNAs to silence those specific targets and prevent metastasis,” Artzi says. “In this way we were able to pinpoint the critical role of these microRNAs in stopping the spread of breast cancer.”

The researchers then developed a method to deliver engineered microRNAs to breast cancer tumors. They embedded nanoparticles containing the microRNAs into a hydrogel scaffold, which they then implanted into mice.

They found that this allowed efficient and precise delivery of the microRNAs to a target breast cancer tumor site. The treatment resulted in a dramatic reduction in breast cancer metastasis, says Artzi.

“We can locally change the cells in order to prevent metastasis from occurring,” she says.

To increase the effectiveness of the treatment even further, the researchers then added the chemotherapy drug cisplatin to the nanoparticles. This led to a significant reduction in both the growth of the primary tumor, and its metastasis.

“We believe local delivery is much more effective (than systemic treatment), because it gives us a much higher effective dose of the cargo, in this case the two microRNAs and the cisplatin,” she says.

“The research offers the potential for combined experimental therapeutics with traditional chemotherapy in cancer metastasis,” says Julie Teruya-Feldstein, a professor of pathology at Mount Sinai Hospital in New York, who was not involved in the study.

The research team, which also includes MIT post doc Joao Conde and graduate student Nuria Oliva, both from IMES; graduate student Avital Gilam and postdoc Daphna Weissglas-Volkov, from Tel-Aviv University; and Eitan Friedman, an oncogeneticist from Chaim Sheba Medical Center in Israel, now hopes to move on to larger animal studies of the treatment.

“We are very excited about the results so far, and the efficacy seems to be really good. So the next step will be to move on to larger models and then to clinical trials, although there is still a long way to go,” Artzi says.

Source: www.linkedin.com

New Project Aims to Set Effectiveness Guidelines for Hemophilia Gene Therapy Trials


New Project Aims to Set Effectiveness Guidelines for Hemophilia Gene Therapy Trials

An international team has joined efforts to establish guidelines for effectiveness and outcome measurements regarding gene therapies in hemophilia.

The CoreHEM project will be led by researchers from McMaster University in Ontario, Canada, in collaboration with the National Hemophilia Foundation (NHF) in the U.S. and the Green Park Collaborative — a major initiative of the Center for Medical Technology Policy (CMTP), based in Baltimore, Maryland.

“With a growing pipeline of gene therapy products for hemophilia, it is an ideal time for this work,” Sean Tunis, president and CEO of CMTP, said in a news release. “This effort will potentially serve as a model for achieving consensus around outcomes to demonstrate effectiveness and value for promising emerging therapies in many other clinical areas, as well as for other rare conditions.”

Hemophilia is caused by a genetic defect that leads to low levels or the total absence of clotting factors — factor VIII in hemophilia A and factor IX in hemophilia B — which are necessary for effective bleeding control. Hemophilia patients need to receive routine injections of the missing clotting factors to control symptoms of the disease. This demanding therapy schedule can have an extreme impact on patients’ quality of life.

Scientific advances have led to the development of new treatments that may have the potential to cure hemophilia A and B by replacing the damaged gene. Clinical trials on these new gene therapies should provide enough evidence demonstrating their effectiveness, but also substantial improvements in reducing or eliminating burdens of the disease.

The CoreHEM project aims to define a core outcome, set through a consensus process, which should be considered when evaluating the effectiveness of gene therapies in patients with hemophilia.

Taking into consideration input from patients, clinicians, researchers, product manufacturers, public and private payers, and U.S. and international government agencies, the team will create a list of potential outcome domains and measurement approaches that will be reviewed by a steering committee.

This list will go through an online Delphi voting process and an in-person consensus meeting to prioritize and condense the list into the final core outcome set.

“These breakthroughs have the potential to be life-changing,” said Val Bias, CEO of the National Hemophilia Foundation. “This collaborative effort will bring a much needed voice from our patients, and the important role they play in identifying outcomes that are vital to their health.”

The final results of the CoreHEM project, expected early in 2018, will be published in a peer-reviewed article providing recommendations for important patient outcomes in clinical studies focused on gene therapies for hemophilia. In addition, an “effectiveness guidance document” will also be published.

Implementing these outcome-defined measures will not only help patients and clinicians to make better treatment-related decisions, but will also potentially improve the way clinical trials are conducted and assessed.

“The enthusiasm from so many stakeholders to becoming part of the project speaks volumes to the potential of this initiative,” said Alfonso Iorio, co-principal investigator and associate professor of health research methods, evidence, and impact at McMaster University.

Creating a consensus for implementation early in the development of breakthrough technology is a key to success, he added.

Physicists Confirm There’s a Second Layer of Information Hidden in Our DNA


IN BRIEF

Theoretical physicists have confirmed that it’s not just the information coded in our DNA that shapes who we are—it’s also the way DNA folds itself that controls which genes are expressed inside our bodies.

We all learned in high school how Watson and Crick pieced together the findings of many scientists to come up with a model of deoxyribonucleic acid (DNA). Information in DNA is stored as code sequences made up of nitrogenous bases. Each cell has the same sequence of codes but executes a different function. Code sequences determine the type of protein to be produced in a certain cell, but it is hypothesized that the mechanical properties of the DNA acts as a second layer of information.

Each cell in our body contains around 2 meters of DNA. But since our cells are so tiny, DNA strands have to be tightly wrapped into bundles called nucleosomes in order to fit.

Learn more about DNA and nucleosomes in the video below:

URL”https://youtu.be/4Z4KwuUfh0A

The folding mechanism of DNA is believed to play a large role in how genes are read by the rest of the cell. Biologists have started to isolate mechanical cues that determine how DNA is folded. Now, theoretical physicists from Leiden University in the Netherlands confirmed through computer simulations that these cues are actually coded into our DNA.

Physicist Helmut Schiessel and his group simulated the folding of DNA strands with randomly assigned cues. The team used genomes of baker’s yeast and fission yeast to find correlations between the mechanics and the actual folding structure of DNA in the two organisms.

The results confirm that this second layer of information exists. This led them to conclude that genetic mutations are not just caused by a change in the sequence of codes but also by a change in the way the strands are folded. This simulation may be helpful in hiding unwanted sequences like those that cause diseases.

 Source:PLOS ONE.

Will we all be tweaking our own genetic code?


You have to wonder what’s going on in the DNA of Harvard genetics professor George Church.

What extra bit of code does he have that the rest of us don’t? If genes tell the story of a person’s life, then some altered sequence of ‘A’s, ‘C’s, ‘G’s and ‘T’s must be at play, because his brain works like almost no one else’s.

About 30 years ago, Prof Church was one of a handful of people who dreamed up the idea of sequencing the entire human genome – every letter in the code that separates us from fruit flies as well as our parents. His lab was the first to come up with a machine to break that code, and he’s been working to improve it ever since.

Once the first genome was sequenced, he pushed the idea that it wasn’t enough to have one sequence, we needed everyone’s. When people pointed to the nearly $3bn price tag for that first one, he built another machine.

Now, the cost is down to below $5,000 per genome, and Prof Church says we’re quickly heading toward another 10- or 20-fold decrease in price – to roughly the cost of a blood test.

Genes: read, write, edit

To Prof Church, routine whole-genome sequencing will herald the beginning of a new era as transformative and full of possibilities as the Internet Age. But this is not just about insurance companies wanting to have every customer’s entire genome in their files.

For Prof Church sees this only as a beginning of the project, rather than the culmination of three decades of work.

Model DNA double helix
Image captionHelping to develop the machines to sequence the human genome was Prof Church’s first big achievement

He’s pointing to at a bigger goal: Now that reading DNA code is almost simple, he wants to write and edit it, too.

He envisions a day when a device implanted in your body will be able to identify the first mutations of a potential tumour, or the genes of an invading bacteria. You’ll be able to pop an antibiotic targeted at the invader, or a cancer pill aimed at those few renegade cells.

Another device will monitor your outside environment, warning you away from sites that pose a health risk.

A range of genetic disorders will be identified at birth, or even conception, and tiny, preprogrammed viruses will be sent into the body to penetrate compromised cells and correct the damage. Changing the adult body at the first signs of illness will be just as easy, he predicts.

There’s no reason, Prof Church says, why people won’t be able to live to be 120, and then 150.

“There used to be this attitude: here’s your genetic destiny, get used to it,” Prof Church says. “Now the attitude is: genetics is really about the environmental changes you can make to change your destiny.”

Democratic science

Standing at 1.93m, with a bushy reddish-grey beard, George Church is hard not to notice. The 57-year-old is both imposing and unassuming. There’s an awkwardness to Church, like an 8th grade boy after a summer growth spurt, and an openness that makes him easy to like. His manner is the same with a Harvard faculty colleague as with the technician operating a machine he helped design.

This democratic instinct comes through in his science. Church advises 20 of the 30-or-so advanced genomics companies in the United States, but his heart is clearly in academia, doing basic science that helps everyone.

As he pushes for the mapping of more and more complete genomes, he also pushes to make those genomes public, so researchers can learn about medical conditions by comparing them. He’s put 11 up on the web already, including his own, and is aiming for 100,000 more.

Once thousands of people with diverse backgrounds have made their genomes and health status public, researchers will be able to delve into a wide range of diseases and disorders, from schizophrenia to heart disease, diabetes to learning disabilities, looking for patterns.

“You bring down the price and many blossoms bloom,” he says.

Prof Church doesn’t want to make these discoveries himself. The pace of that kind of science is too slow for him, and not driven by technology.

George Church
Image captionProf George Church at the Wyss Institute for Biologically Inspired Engineering at Harvard

‘Evolution on steroids’

There’s a climate-controlled room in the middle of Church’s generous lab space, where a small tray shakes back and forth, jostling pellets of E. coli DNA.

In a four-hour production process, researchers can turn on or off a single base pair of that DNA, or whole regions of genes to see what happens. The goal is to find a way to improve production of industrial chemicals or medications, or to test viral resistance.

“You could think of this as driving evolution to very rapid rates,” Church said. “Sort of evolution on steroids.”

The machine is a second-generation Multiplex Automated Genome Engineering (MAGE) machine, built with help from industry; the first one, which sits across the street not far from Church’s corner office was a doctoral student’s PhD thesis. Another thesis project sits just on the other side of the wall from new MAGE. Called the Polonator, this open-source genome-sequencing machine can read and write a billion base pairs at a time.

These two machines put Church’s lab at the forefront of synthetic biology, a burgeoning new field that aims to make things Mother Nature never thought of, like high efficiency, non-polluting fuels, and viruses that can carry cancer drugs safely to a tumour.

With these machines, Prof Church is doing to synthetic biology what he’s already done to personalised genomics: making it cheaper, faster and available to everyone.

model of a DNA strand
Image captionTake a snip of DNA here, insert a snip of DNA there

Ethical concerns

“He’s beginning to transform synthetic biology to a larger scale,” says James J. Collins, a professor at Boston University and Prof Church’s colleague at the Wyss Institute for Biologically Inspired Engineering at Harvard.

Prof Collins acknowledges that some people will have ethical concerns about scientists writing genetic codes. But, he said, the reality of synthetic biology is nowhere near as scary as the hype. No one is creating doomsday species or humanoids. They’re just barely able to create a single new cell, says Prof Collins.

“I think we as a community have a need and a role and responsibility to educate the public as well as to take precautionary safeguards to make sure we’re not introducing something that’s problematic,” says James Collins, who builds his cells with programmable kill switches, so they self-destruct before reproducing or mutating.

George Annas, chairman of the department of health law, bioethics and human rights at Boston University, agrees that it’s too early to be troubled by the ethics of synthetic biology. “At this point, we don’t know how synthetic biology will turn out or even if it will work at all,” he says.

Of the possible fears about new life forms: “I think we’re in the realm of science fiction right now,” Mr Annas says.

Reality check

Prof Church’s optimism about the power of reading and writing DNA is contagious, but not irresistible.

“You need George’s imagination and his vision if you’re going to do make any progress at all. But you’ve got to be foolish to think you’re going to make as much progress as he [imagines],” Mr Annas says.

American medical care is going broke as it is, he said. Adding more personalised treatment is only going to drive up the cost. And medicine may be able to add years to someone’s life, but the quality of those years is unlikely to be good, warns Mr Annas.

Chad Nussbaum agrees.

“There’s a statistical chance of being hit by a truck that’s going to make it hard to live to 150 no matter how healthy you are,” says Mr Nussbaum, co-director of the genome sequencing and analysis program at the Broad Institute of Harvard and MIT, a genetics research institute, where Church is an associate member.

Extreme aging isn’t all about genetics, Mr Nussbaum says, it’s basic engineering: parts just wear out over time. “It’s wonderfully naive to think all we have to do is learn all the genetics and we’ll live to be 150.”

But Chad Nussbaum says he still admires Prof Church’s vision and his “genius.”

“It’s a great thing to think big and try to do crazy things,” says Mr Nussbaum. “If you don’t try to do things that are impossible, we’ll never accomplish the things that are nearly impossible.”

How Close Are We to Successfully Cloning the First Human?


When Will We Clone a Human?

Human cloning may endure as one of the go-to science fiction tropes, but in reality we may be much closer to achieving it than our fictional heroes might imply. At least in terms of the science required. On of the most prominent hurdles facing us may have less to do with the process and more to do with its potential consequences, and our collective struggle to reconcile the ethics involved. That being said, while science has come a long way in the last century when it comes to cloning a menagerie of animals, cloning humans and other primates has actually proven to be incredibly difficult. While we might not be on the brink of cloning entire human beings, we’re already capable of cloning human cells — the question is, should we be?

Seeing Double: The History of Animal Cloning
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The astoundingly complex concept of cloning boils down to a fairly simple (in theory, at least) practice: you need two cells from the same animal — one of which is an egg cell from which you’ve removed the DNA. You take the DNA from the other somatic cell and put it inside the devoid-of-DNA egg cell. Whatever that egg cell goes on to produce for offspring will be genetically identical to the parent cell. While human reproduction is the result of the joining of two cells (one from each parent, each with their own DNA) the cellular photocopy technique does occur in nature. Bacteria reproduce through binary fission: each time it divides, its DNA is divided too so that each new bacterium is genetically identical to its predecessor. Except sometimes mutations occur in this process — and in fact, that can be by design and function as a survival mechanism. Such mutations allow bacteria to, for example, become resistant to antibiotics bent on destroying them. On the other hand, some mutations are fatal to an organism or preclude them coming into existence at all. And while it might seem like the picking-and-choosing that’s inherent to cloning could sidestep these potential genetic hiccups, scientists have found that’s not necessarily the case.

Prediction: When will the first human be cloned?

What The Experts Say

While Dolly the sheep might be the most famous mammal science has ever cloned, she’s by no means the only one: scientists have cloned mice, cats, and several types of livestock in addition to sheep. The cloning of cows has, in recent years, provided a great deal of knowledge to scientists about why the process doesn’t work: everything from implantation failure to those aforementioned mutations that render offspring unable to survive. Harris Lewin, professor in the UC Davis Department of Evolution and Ecology, and his team published their findings on the impact cloning has on gene expression in the journal Proceedings of the National Academy of Sciences back in 2016. In the study’s press release Lewin noted that the findings were certainly invaluable to refining cloning techniques in mammals, but that their discoveries “also reinforce the need for a strict ban on human cloning for any purposes.”

The creation of entire mammals via reproductive cloning has proven a difficult process both practically and ethnically, as legal scholar and ethicist Hank Greely of Stanford University explained to Business Insider in 2016:

“I think no one realized how hard cloning would be in some species though relatively easy in others. Cats: easy; dogs: hard; mice: easy; rats: hard; humans and other primates: very hard.”

The cloning of human cells, however, may be a far more immediate application for humans. Researchers call it “therapeutic” cloning, and differentiate it from traditional cloning that has reproductive intent. In 2014, researchers created human stem cells through the same cloning technique that generated Dolly the sheep. Because stem cells can differentiate to become any kind of cell in the body, they could be utilized for a wide variety of purposes when it comes to treating diseases — particularly genetic diseases, or diseases where a patient would require a transplant from an often elusive perfect match donor. This potential application is already well underway: earlier this year a woman in Japan suffering from age-related macular degeneration was treated with induced pluripotent stem (iPS) cellscreated from her own skin cells, which were then implanted into her retinas and stopped her vision from degenerating further.

We asked the Futurism community to predict when they think we’ll be able to successfully clone a full human, and the majority of those who responded agree that it feels like we’re getting close: nearly 30 percent predicted we’ll clone our first human by the 2020s. “We have replaced, and replicated almost every biology on earth,” said reader Alicja Laskowska, “[the] next step is for cures and to do that you need clean DNA, and there’s your start.”