July 28, 2017
Last week we heard that for the first time in the U.S. a human embryo was genetically edited. The event happened in Oregon. The lead scientist is Shoukhrat Mitalipov.
Most of the action in FOXP5, the novel I wrote with my undergraduate roommate, David Deamer, takes place in Kazakhstan. Dr. Mitalipov was born in Kazakhstan in 1961. Like the principle scientist in the novel, Mitalipov is a leading figure in manipulating stem cells, eggs, and embryos. Unlike that scientist, he is an ethical man.
Fortunately, life doesn't always imitate art.
With gene editing becoming cheaper, more reliable, and easier the speculation about creating human GMOs intensifies. The news from Amsterdam of the discovery of 40 genes that influence human intelligence will fuel even more speculation. It will also create sensationally exaggerated headlines.
The genes, in fact, account for only 5% of the variation in human intelligence. A recent report on the research includes this:
But research on the genetics of IQ has always raised serious questions about how the information might be used. Could human embryos be chosen according to their future brain power? Could scientists make drugs to enhance human intelligence? If so, would only the richest have access to such powerful technology? “There is always the question of designer babies and can we use this knowledge to improve intelligence,” said Posthuma. “These are valid questions, but it’s very far from where we are now. You certainly wouldn’t be able to design a baby based on the current knowledge.”
Such uses are on the horizon. IVF embryos are already screened for genetic faults. With larger studies, scientists expect to find more genes that contribute to intelligence. Eventually, the work may reach a point where the genomes of IVF embryos could be used to rank them according to their intellectual potential, even if the difference is so small as to be insignificant. “You can imagine that as soon as it becomes possible to explain a good deal of the variance in intelligence, people are going to start doing this,” said Stuart Ritchie, a researcher in cognitive ageing at Edinburgh University and author of the book Intelligence: All that Matters.
The prospect of IQ-boosting drugs should not be dismissed either, Ritchie added.
For the full article see: https://www.theguardian.com/science/2017/may/22/scientists-uncover-40-genes-iq-einstein-genius?utm_source=esp&utm_medium=Email&utm_campaign=Lab+notes+2016&utm_term=228132&subid=20984534&CMP=ema-3242
If you see GMOs as a big disruptive force and the most complex issue in bio-ethics, you are out of date. Synthetic biology makes GMOs look simple.
Have no doubt that humans of the near future will be genetically modified organisms--either by gene editing or gene splicing or both. Having healthy childen has become more and more certain, but what child will emerge from preganancy still has a large element of risk and chance.
Not only healthy children, but children with certain characteristics and advantages is a demand that will break through legal, regulatory and ethical barriers. That's just the way human history happens.
Below is some of the latest news relevant to this issue.
From Disease to DesignJan 09, 2017CRISPR, like IVF and other technologies before it, raises the specter of the creation of "designer babies," writes Philip Ball at the Guardian.
Though CRISPR/Cas9 is being explored as a way to modify disease-causing genes, there's the concern that the tool could be used for non-therapeutic purposes, he adds. But a number of researchers and ethicists don't think CRISPR-driven human reproduction will be a concern anytime soon as it's too expensive and has unknown health risks.
Instead, Stanford University's Hank Greely tells Ball that pre-implantation genetic diagnosis coupled with embryo selection is the current most plausible route for the development of "designer babies." Such an approach is already used by a small percentage of couples seeking in vitro fertilization to screen for diseases like thalassemia or cystic fibrosis. Even this approach, though, isn't a good way to "design" babies, Greely tells Ball, as it requires egg harvesting, which is risky and doesn't yield that many eggs. However, he adds that will change with developments in the field and with cheaper genome sequencing.
Still, Ball notes that many traits have turned out to be more complicated than initially assumed — numerous genes influence, for instance, diabetes risk and little is known about genes that may affect intelligence. Designing, then, may be limited and give probabilistic predictions like that a child would have a 60 percent chance of being in the top half at school, he adds.
While Greely predicts it'll take a few decades for gene editing and reproductive tools to be used for genetic enhancements, Alta Charo from the University of Wisconsin tells Ball that it may never become common for people who aren't facing serious diseases or infertility. "[W]e already have evidence that people do not flock to technologies when they can conceive without assistance," she says.
Several years ago when we began writing and research for FOXP5 I occasionally wrote about my increasing awareness of how genetic engineering could be used by rogue nations and terrorists.
Last week President Obama's science and security advisers urged him to rapidly create a bio-defense program that might reduce our vulnerability. Their letter is worth reading. This is an issue that President Obama and President-Elect Trump should collaborate on now.
Here is a key passage from the advisers' letter followed by the URL for the entire text as well as the URL for an article from the MIT Technology Review.
"We, your President’s Council of Advisors on Science and Technology (PCAST), urge you to take immediate action to ensure that the Nation has the ability to meet these challenges. In this letter, we recommend measures aimed at decreasing the probability and impact of a future biological attack against the United States. Our recommendations are divided into actions with near-, medium-, and long-term goals.
All of these actions should be undertaken now to ensure that the capabilities will be ready when needed."
GENE EDITING FOR DUMMIES--this title does not exist but we are now close to having gene editing available to the kids next door as well as terrorists, rogue nations, and mad scientists.
I've noted several times in the past year that one of the developers of the easiest gene editing process has said such a lab could be available for less than $2,000. That may be way over-priced.
Below are excerpts from an article about a new study of gene editing availability and its consequences. Homo sapiens is rapidly acquiring the powers to become Homo divinus.
[A study by Nuffield Council on Bioethics ] found that the materials needed to perform basic experiments were available to enthusiasts outside academia and established labs. This year, one firm began to sell a kit for £100 to DIY biology interest groups that allowed them to render the common soil microbe, E coli, resistant to the antibiotic streptomycin.
The report goes on to say that genetic technology has become so powerful that nations need to decide whether or not doctors should ever be allowed to modify the human species.
While the creation of GM humans is not on the horizon yet, the risks and benefits of modifying a person’s genome - and having those changes pass on to future generations - are so complex that they demand urgent ethical scrutiny, the review found.
“This could transform our range of expectations and ambitions about how humans control our world,” said Andrew Greenfield, a geneticist and chair of the Nuffield Council’s working group. “Although most uses so far have been in research, the potential applications seem to be almost unlimited.”
. . .
Because Crispr-cas9 does not leave any traces, meat and other products from GM animals could find its way to market without being labelled. Meanwhile, the simplicity and low cost of Crispr-cas9 means amateurs in the home can now perform their own experiments.
. . .
Scientists have already begun to edit the genes of human embryos, but only for basic research. Earlier this year, researchers in China tried to add HIV resistance to human IVF embryos which had been donated to science when tests found them to be unviable. The experiments did not achieve their goal, but highlighted how difficult the procedure was likely to be in humans.
In 2015 another Chinese team became the first in the world to edit human embryos, when they tried, and failed, to modify a gene that causes beta-thalassaemia, a potentially fatal blood disorder. Again, the work was performed on abnormal IVF embryos donated to research.
[Kaufman’s note: the author does not cite any source for the claim that the embryos were abnormal IVF embryos and donated for research. Viable embryos would be easy to find. Without inviting any political debate, I suggest readers recall the debate about aborted embryos at Planned Parenthood, simply as an example of one potentially large source of viable embryos--abortion.]
. . .
The report notes that in the future, it may be possible to enhance people with genes from other organisms, for example to improve night vision and sense of smell.
“It is only right that we acknowledge where this new science may lead and explore the possible paths ahead to ensure the one on which we set out today is the right one,” said Yeung.
Gene editing cures blindness--that's the hope behind the news that scientists have restored sight to blind mice. The way they did it validates the science readers find in The Hunt For FOXP5. "The condition, which affects about one in 4,000 people, occurs when a faulty gene causes retinal cells to gradually die off, leading to blindness. The scientists targeted the retinal cells by injecting a virus, carrying a package of gene-editing instructions, into the eyes of blind three-week-old rats."
Instead of revealing the plot, I leave it to readers to find the parallels.
The URL for the article on gene editing and blindness is: https://www.theguardian.com/science/2016/nov/16/breakthrough-as-gene-editing-technique-restores-sight-to-blind-animals
Today's news brings a bold prediction from one of the leaders in genome sequencing, Oxford Nanopore Technologies. (Disclosure: David Deamer, a co-author of this book, is an adviser to ONT and played a key role in the company's breakthrough in using nanopores to sequence genomes.)
If you thought computing power developed rapidly, consider this from the conclusion of the article below: "the genomic revolution is moving three times faster than Moore’s Law at the least"
[posted by Wallace Kaufman]
Oxford Nanopore Expands Sequencing and CRISPR Applications
Oxford Nanopore (ONT) - a private company and potential competitor to Illumina, PacBio, and Qiagen - announced a number of groundbreaking developments in the field of sequencing technology this week. In addition to new pores, new chemistries, and updates on various devices, CTO Clive Brown detailed a CRISPR-based Cas9 enzyme application that the company plans to commercialize with mobile sequencers. Although it has overpromised and under-delivered for the past four or five years, ONT could become a disruptive innovator in the sequencing market if it is able to commercialize even half of the new products and services – importantly those based on CRSPR – it featured this week.
ARK believes that a CRSPR-based Cas9 application to enrich DNA in silico could be the next significant breakthrough in sequencing technology, causing another step function decline in time and costs. With a probe RNA molecule, ONT has disabled the Cas9 cutting activity and enriched DNA in silico in order to sequence specific regions of DNA: it calls this breakthrough “on-demand” sequencing. ONT also plans to commercialize pre-packaged probe kits for both protein detection and molecular diagnostic tests. That said, “on-demand” sequencing must make significant leaps in both specificity and sensitivity to become truly disruptive to existing platforms in the market during the next few years.
ONT’s pore technology is another candidate for disruptive innovation in this space, thanks to its base-calling accuracy. The R9.4 can now sequence 450 bases/second, an 80% improvement in speed without comprising accuracy, compared to previous generations. Using recurrent neural networks (RNNs) instead of the traditional Hidden Markov Model (HMM), ONT can train the sequencer to read chromatogram data more accurately into nucleobases (the sequence of nucleic acid in DNA), recognizing homopolymers. Oxford Nanopore’s signal analysis with neural networks is a fast moving new field with cutting edge algorithms. Combined with field-programmable gate arrays (FPGAs), RNNs could turbocharge sequencing efficiencies.
Brown revealed that one of its long term goals is to create a one million channel sensor which, at a 100% yield rate, could sequence a human genome in as little as three minutes. Today’s state of the art machines sequence the approximately ~3 billion base pairs of DNA in human genomes in one to three hours. Because the genomic revolution is moving three times faster than Moore’s Law at the least, ARK is keeping a close eye on this space!
What's It Like For A Working Scientist To Write A Novel?
By Dave Deamer | July 28th 2016
In an essay for The New York Times, (September 28, 2002) Joseph Epstein wrote: "According to a recent survey, 81 percent of Americans feel they have a book in them -- and that they should write it. As the author of 14 books, with a 15th to be published next spring, I'd like to use this space to do what I can to discourage them."
Christopher Hitchens had a similar sentiment: “Everybody does have a book in them, but in most cases that's where it should stay.”
Despite that advice, I decided to write a book, a novel, and I’m here to recommend the exercise. I have been active in research for many years, and all that time a question has been niggling in the back of my mind, inspired by the discovery of a mutation in the FOXP2 gene that seemed to accompany the emergence of Homo sapiens from other primates 200,000 years ago. Could a similar mutation emerge in today's human genome and somehow give rise to a dominant new species? With the powerful methods now available in cell and molecular biology, it might even be possible to engineer a discontinuity in human evolution in a single generation, rather than the usual million years.
So I wanted to use a fictional narrative to see how that might play out. I would call the mutant gene FOXP5, fictional of course, yet at least plausible. Thus the inspiration, but the hard work lay ahead. I needed a co-author.
Now I need to tell you about Wallace Kaufman. Wallace and I were friends and roommates at Duke University. After we graduated in 1961, Wallace went on to Oxford as a Marshall Scholar, earned an M.Litt., then returned to become a member of the faculty at UNC-Chapel Hill for nine years. I took my Ph.D. at Ohio State University in biochemistry followed by post-doctoral research at UC Berkeley. We didn't see each other again for many years, but kept in touch sufficiently to know where we were in our careers. Wallace left academia, dividing his time between writing and consulting on land usage and property valuation, including a stint with the U.S. Agency for International Development in Kazakhstan. I became a faculty member at UC Davis in 1967, then moved to UC Santa Cruz in 1994.
In 2001, I attended the 40th reunion of our Duke class of 1961 and had time to visit Wallace at the owner-built home he wrote about in his memoir, Coming Out of the Woods. He was in the process of selling the house and surrounding acreage, planning to move to Oregon where he now resides in a secluded home just outside Newport. Three years ago, while relaxing during the Christmas holidays, it occurred to me that with Wallace nearby if might be interesting to see if a former English professor would enjoy co-authoring a novel that explores what it would be like to be the sole example of the next human species. Something like this had been done earlier by Olaf Stapleton in his book Odd John, but that was written nearly a century ago. An updated version of the concept seemed timely.
Wallace was agreeable and eager to write fiction again. He had written short stories for literary magazines as well as Redbook and Mademoiselle, but nothing book length. We both had a lot of experience writing multiple non-fiction books. The idea was that I would provide the science background and Wallace would provide literary value. We began to toss ideas back and forth by email. We built plot, characters, and locations on our personal experiences.
Because of Wallace's extensive work in Kazakhstan, we decided to set much of the plot there. From my experience as a working scientist we also developed the character of Professor Michelle Murphy, a molecular geneticist at the University of Oregon whose research specialty is development of the nervous system. From both our experiences adopting children, mine from Russia, Wallace from Kazakhstan, we decided that Michelle would adopt an infant daughter from a Kazakhstani orphanage, and this would turn out to be the mutant child featured in the narrative.
It was my job to add the scientific foundation of the novel. This began in the first chapter with Michelle lecturing to an audience of students and faculty about the discovery of a human bone in an Ethiopian dig. When a sample of DNA extracted from the bone is analyzed, it has the human FOXP2 gene, so the bone is the first direct evidence that our ancestors were roaming Africa nearly 200,000 years ago. The second chapter continues the story by going back in time and describing the life of Ma, the first primate with the FOXP2 mutation who was the first member of the human species.
In the third chapter, Michelle is visited by a CIA agent and learns that she will soon be invited to give a lecture at an international meeting in Astana, the new capital of Khazakhstan. The agent tells her that her host will be Arman Akenov, a brilliant Khazakh geneticist who is cloning race horses. During the Soviet era he worked with the biological warfare lab on an island in Kazakhstan’s Aral Sea. He recently ordered SV 40, a virus known to cause cancerous transformation of human cells, and the agent is concerned that Akenov may be developing a biological warfare weapon. He asks Michelle to report back if she sees anything that might be relevant. She agrees to do this, accepts the invitation and travels to Astana with her adopted daughter. Michelle gives her lecture, but when she tries to return home she is told at the airport that the adoption was illegal and her daughter must remain in Kazakhstan until the legal problem is straightened out.
The rest of the book tells how Michelle finally rescues her daughter. Without giving too much away, it involves her ability to design a viral vector that can deliver the FOXP5 gene to the neurons of the cerebral cortex in a human brain. As you might imagine, this is likely to be very dangerous. The ethical questions of creating a trans-human are labyrinthine.
There is a happy ending, both for the book and for its authors. Springer is a Swiss publisher with thousands of books in print, mostly dealing with scientific topics but also including a small section called Science and Fiction where The Hunt for FOXP5 has been published. Last month Wallace and I enjoyed seeing our book advertised as a paperback at Amazon, already with a couple of five star reviews. Another positive review was published on the website of a knowledgeable science blogger. Even better, my brother said he liked it and my daughter came in and gave me an unexpected hug when she finished reading the final prepublication draft.
Wallace and I positively enjoyed the give and take of being co-authors. The most interesting thing about the writing process is how the characters began to come alive in our heads in unpredictable ways, and the surprising twists that emerged spontaneously in the narrative, So, if you are among the 81% of Americans who are thinking about writing a book, go ahead and get started, it will give your brain a workout, and you and your audience will discover things in there you never imagined.
Until you did.