gene editing

Here’s Why Many CRISPR/Cas9 Experiments Could Be Wrong – and How to Fix Them

Researchers assumed that CRISPR was turning off genes. They shouldn’t have.

Every living cell on Earth has proteins. Typically thousands of them, that serve as molecular machines to digest food, sense the environment, or anything else a cell must do. However, many genes, and the proteins they code for, have unknown functions. In humans, the function of about 1 out of 5 of genes is unknown. To explore these dark corners of the genome, scientists can break up DNA to disable a gene, making their encoded proteins nonfunctional, and watch what happens to cells as a result, inferring the lost function from what goes wrong.

When CRISPR/Cas9 came online in 2012, it offered scientists a tool to do exactly this – cut genes. The Cas9 enzyme searches through DNA, using a “guide RNA” to look for a specific sequence, and makes a cut when it finds a match. The gene, split in two, is repaired by the cell, but often with a large chunk missing. Many scientists assume that if a chunk of a gene is missing then the protein that it encodes will not function, or even be produced.

Researchers at the European Molecular Biology Laboratory in Heidelberg, Germany used CRISPR to make cuts in 136 different genes. In about a third of cases, proteins were still produced from these “damaged” genes and, furthermore, many of the proteins remained partially functional. This strange phenomenon, of damaged DNA producing functional protein, does more than punctuate life’s remarkable adaptability and resilience.

It means that dozens, or hundreds, of studies that used CRISPR/Cas9 to knock out genes, but failed to validate that the encoded protein was fully removed, could be incorrect or misleading.

Also read: How Gene Editing Is Changing the World

While many labs that use CRISPR to knock out genes do validate that the encoded protein is no longer produced, other labs fail to check. Searching for one protein in a cell is time-consuming and technically challenging; testing for protein function takes even longer. There are some methods available to look for specific proteins, but many CRISPR/Cas9 studies fail to run these experiments – or scientific journals don’t ask for the data.

While many labs that use CRISPR to knock out genes do validate that the encoded protein is no longer produced, other labs fail to check.

Nature Methods, the same journal that published the paper from the Heidelberg laboratory, recognised shortcomings in CRISPR validation early on. In 2017, they highlighted a genome-editing consortium, in collaboration with the US National Institute of Standards and Technology, that aims to develop standardized procedures for CRISPR research, including publishing guidelines that include which guide RNAs were tested, how they were designed, and which controls were used in experiments.

The problem with major scientific developments, especially CRISPR/Cas9, is that experimental tools often explode in popularity before scientists and editors can implement standard procedures. When DNA sequencing was developed in the 1970s, for instance, there was little need for standards because it was so challenging to decipher the sequence of even a short piece of DNA. A decade later, however, GenBank, a DNA sequence repository, came online and journals began to mandate that researchers deposit their sequences. This requirement, together with reporting standards issued by journals like Nature, have ensured that a rapidly growing collection of DNA sequences can be vetted and independently analysed by the scientific community. The same is true for methods like x-ray crystallography, with journals requiring that protein structures be independently validated and uploaded to publicly-accessible databases.

But while some scientists were shocked by the new study, others took a laissez-faire approach to the findings. On Twitter, many vented their rage at what they felt was a lack of careful controls by the scientific community. Raphael Ferreira, a postdoctoral fellow at Harvard Medical School, was inspired, perceiving this study as a game changer for the CRISPR community.

“I was as surprised by the results in a really positive way, as this paper rings the wake-up call for every scientist using CRISPR/Cas9,” Ferreira said.

Despite the enthusiasm, however, Ferreira will not change how he performs his own experiments. “The few times I have [used CRISPR/Cas9] in mammalian cells, I have always confirmed them with a Western blot,” referring to an experimental method to detect specific proteins.

Victor de Lorenzo, a research professor at the National Center for Biotechnology in Madrid, agreed, claiming that, “…the only way to ensure that a protein is altogether removed is by making a Western blot.”

Down the hall or across the street from my office, dozens of scientists use CRISPR/Cas9 to uncover protein functions. One of these researchers is Shashank Gandhi, a PhD student at the California Institute of Technology (CalTech) that has published CRISPR/Cas9 methods to delete genes in chicken embryos. Though he agrees with Ferreira and de Lorenzo, Gandhi asserts that validations could be taken a step further, and believes that journal editors should take action.

Also read: Is There More to Gene Editing Than Creating ‘Designer’ Humans?

“I think that journal editors should encourage authors to present supplemental data on how the knockouts were validated,” insists Gandhi. “I know that Nature requires that information as part of a “research summary” document that is submitted to the journal with each paper submission.”

If Nature, which is widely considered the premier academic research journal, takes action to ensure that CRISPR knockouts are validated, then perhaps other publishers will take notice. In the meantime, Gandhi and others are not taking any chances.

“I use several approaches to validate my CRISPR knockouts. For starters, I design and test multiple [guide RNAs] targeting the same gene for all my knockout experiments. Secondly, wherever applicable, I try to perform rescue experiments to establish loss of function phenotypes,” says Gandhi, referring to an experiment in which a deleted gene is restored to test whether that protein’s phenotype returns, confirming a link between a gene and the function that was lost when the gene was broken.

While all of the scientists that I spoke with agreed that researchers could do more to double check their experiments, it is unclear what actionable steps could be taken. Perhaps a combination of scientific, academic, and institutional changes could alleviate the potential for misleading studies. Faster experimental methods to detect proteins, standardised publishing procedures, and an academic database that describes which guide RNAs have been tested in each organism, would all serve to enhance the rigour of current studies.

Unfortunately, academic institutions and scientific publishers are hulking bureaucracies with slow-moving policy changes. Ensuring that CRISPR/Cas9 produces repeatable experiments – rather than blemishes on the scientific record – will require the collective action of scientists. It will demand self-governance.

Nicholas McCarty, Bioengineering, California Institute of Technology

This article was published in MassiveScience. Read the original here.

How Gene Editing Is Changing the World

In ‘Hacking the Code of Life’, Nessa Carey explores advances that are giving us new powers to alter the genome.

Across the US, more than 100,000 people are awaiting organ transplants. But there simply aren’t enough hearts, lungs, livers, and kidneys to meet demand, and 20 people die every day without the organs they need. For decades, scientists have dreamed of using animals to help fill the gap. They’ve been particularly interested in harvesting organs from pigs, whose physiology is similar to our own. Unfortunately, pigs also present some big biological challenges, including the fact that their genomes are chock full of genes that code for what are known as retroviruses, which could pose a serious threat to patients who receive porcine organs.

In 2015, George Church, a geneticist at Harvard University, announced a stunning breakthrough: Working with pig cells, he and his colleagues had managed to disable 62 copies of a retrovirus gene in one fell swoop. “This would have been virtually impossible and a logistical nightmare with older forms of genetic modification,” writes Nessa Carey in her new book, Hacking the Code of Life: How Gene Editing Will Rewrite Our Futures. But by using the new gene editing technology known as Crispr, the task was a relative cinch.

Nessa Carey
Hacking the Code of Life
Icon Books

It’s just one example of how gene editing is giving us the power to alter the genome with unprecedented speed and precision. Carey, a biologist with a background in the biotech and pharmaceutical industry, offers a brisk, accessible primer on the fast-moving field, a clear-eyed look at a technology that is already driving major scientific advances – and raising complex ethical questions

“It’s giving every biologist in the world the tools to answer in a few months questions that some scientists have spent half their careers trying to address,” Carey writes. “It’s fueling new ways to tackle problems in fields as diverse as agriculture and cancer treatments. It’s a story that began with curiosity, accelerated with ambition, will make some individuals and institutions extraordinarily wealthy, and will touch all our lives.”

Though there are several different approaches to gene editing, the most prominent – and the one that really supercharged the field – is Crispr. The technique, based on an anti-viral defence system that’s naturally present in bacteria, requires two pieces of biological material: an enzyme that acts as a pair of minuscule scissors, slicing strands of DNA in two; and a guide molecule that tells the enzyme where to cut.

In bacteria, these guide molecules direct the enzyme to chop up the genomes of invading viruses, preventing them from replicating.

But in 2012 and 2013, two teams of scientists reported that it was possible to hack this system to slice into any strand of DNA, at any complementary location they chose. Researchers could, for instance, create a guide molecule that steered the enzyme to one specific gene in the mouse genome and insert the editing machinery into a mouse cell; the enzyme would then make its cut at that exact spot.

Also Read: Is There More to Gene Editing Than Creating ‘Designer’ Humans?

The cell would repair the severed DNA, but it would do so imperfectly, disabling the gene in question. In the years that followed, scientists refined the technique, learning to use it not only to inactivate genes but also to insert new genetic material at specific locations along the genome.

The approach is cheaper, easier, and faster than older methods of genetic engineering, which were first developed in the 1970s. In addition, as Carey explains, “it can be used to create smaller modifications to the genome, and leaves fewer extraneous genetic elements. In its most technically exquisite form, gene editing leaves no molecular trace at all. It may just change, in a precisely controlled manner, one letter of the genetic alphabet.”

missing heritability problem, gene variants, rare diseases, genome wide association studies, whole genome sequencing, DNA sequencing, body mass index, human body height, polygenic risk score, preprint paper, peer review, genetic variation, heritability,

But in 2012 and 2013, two teams of scientists reported that it was possible to slice into any strand of DNA. Photo: qimono/pixabay

The applications are almost endless. Gene editing has immense potential for basic research; scientists can learn a lot about what genes do by selectively disabling them. In addition, researchers have used the technology to create a wide variety of organisms that could become valuable agricultural commodities, including mushrooms that don’t brown; wheat that produces fewer gluten proteins; drought tolerant, high-yield rice and corn; disease-resistant pigs; and super muscular goats.

How these products will do on the market – if they ever reach it – remains uncertain. Globally, gene-edited organisms are regulated by a patchwork of conflicting rules. For instance, in 2018, the US Department of Agriculture announced that it would not regulate gene-edited crops that “could otherwise have been developed through traditional breeding techniques.” A few months later, however, the European Union said that it would subject gene-edited plants to stringent restrictions.

Beyond agriculture, gene editing has enormous potential for medicine. It might, for instance, become a much-needed treatment for sickle cell disease. That painful, debilitating disease results from a genetic mutation that causes patients to produce a deformed version of haemoglobin, a protein that helps red blood cells transport oxygen. In a clinical trial currently underway, scientists are removing stem cells from the bone marrow of sickle cell patients, using Crispr to edit them, and then infusing the edited cells back into patients.

Also Read: Explainer: What Is CRISPR and How Does It Work?

Even if this trial succeeds, however, gene editing will not be a cure-all. It doesn’t always work perfectly and can be challenging to administer directly to living humans (which is why some scientists are instead editing patients’ cells outside the body). Moreover, many diseases are caused by complex interactions between multiple genes, or genes and the environment. “In fact, many of the most common and debilitating conditions aren’t likely to be good candidates for gene editing any time soon,” Carey writes.

And, of course, the ethics of human gene editing can be enormously fraught. That’s especially true when scientists modify sperm cells, egg cells, or early embryos, making tweaks that could be passed down to subsequent generations. This kind of gene editing could theoretically cure some absolutely devastating genetic conditions, but we still have a lot to learn about its safety and effectiveness. It also raises a host of difficult questions about consent (an embryo obviously cannot give it), inequality (who will have access to the technology?), and discrimination (what will the ability to edit a gene related to deafness mean for deaf people, deaf culture, and the disability rights movement more broadly?).

Even in the face of these questions, at least one scientist has already forged ahead. In November 2018, He Jiankui, a researcher then at the Southern University of Science and Technology in China, shocked the world by announcing that the world’s first gene-edited babies – twin girls, who He called Nana and Lulu – had already been born. Months earlier, when Nana and Lulu were just embryos, He had edited their CCR5 genes, which code for a protein that allows HIV to infect human cells. By disabling the gene, He hoped to engineer humans who would be protected from HIV infection.

Also Read: How a Rogue Chinese Experiment Might Affect Gene-Based Therapies in India

The outcry was swift and harsh. Scientists alleged that He’s science was sloppy and unethical, putting two human beings at unnecessary risk. After all, there are already plenty of ways to prevent HIV transmission, and the CCR5 protein is known to have some benefits, including protecting against the flu. And He had raced ahead of the experts who were still trying to work out careful ethical guidelines for editing human embryos. “He Jiankui has shot this measured approach to pieces with his announcement, and now the rest of the scientific community is on the back foot, trying to reassure the public and to create consensus rapidly,” Carey writes.

Scientist He Jiankui attends the International Summit on Human Genome Editing at the University of Hong Kong on November 28, 2018. Photo: REUTERS/Stringer/File Photo

Hacking the Code of Life doesn’t break much new ground, and for readers who have been paying attention to Crispr over the past few years, little in the book will come as a surprise. But it does provide a broad, even-handed overview of how much has already happened in a field that is less than ten years old.

Carey swats down the most dystopian dreams about Crispr, like the prospect that criminals might edit their own DNA to evade justice. She’s similarly skeptical that we’ll end up using the technology to create “super-beings with enhanced genomes that will make them taller, faster, more attractive.”

“We actually understand very little about the genetic basis of these traits and what we do know suggests that it will be very difficult to enhance humans in this way,” she writes.

But she also acknowledges real risks, including the possibility that the technique could be used to create dangerous bioweapons, that gene-edited organisms could destabilise natural ecosystems, and that our new, hardy crops could prompt us to convert even more of the Earth’s undeveloped places into farmland.

None of this means that the technology should be abandoned; it has immense potential to improve our lives, as the book makes clear. But it does mean we need to proceed with caution. As Carey writes, “Ideally, ethics should not be dragged along in the wake of scientific advances; the two should progress together, informing one another.”

Emily Anthes, who has written for Undark, The New York Times, The New Yorker, Wired, and Scientific American, among other publications, is the author of the forthcoming book The Great Indoors.

This article was originally published on Undark. Read the original article.

Were the Brains of China’s CRISPR Twins Inadvertently ‘Enhanced’?

He Jiankui attempted to remove a gene called CCR5 to build resistance to HIV in two babies. New research has found that the same ‘edit’ has other consequences.

New Delhi: A Chinese scientist who created an international controversy by claiming to have made the world’s first genetically edited babies may also have inadvertently boosting their memory and cognition.

<>Chinese researcher He Jiankui claimed to have modified the genes of twins Lulu and Nana before their birth, using the gene-editing tool called CRISPR. While He said his intention was to help the babies resist HIV better, new research says it may have affected the babies’s brains as well.

CRISPR can identify and cut specific sections of a gene and remove it from the sequence. It has the potential to remove faulty genes that result in undesirable mutations and can be used to treat diseases.

However, research has been limited to treating existing conditions in adult patients and not to engineer “super-babies”. This is primarily because not enough is known about the DNA or the chemistry to improve them. Most countries have banned genetic editing of human embryos. Even in China, it’s illegal to edit embryos that are over 14 days old.

Also Read: How a Rogue Chinese Experiment Might Affect Gene-Based Therapies in India

He, the Chinese researcher, attempted to remove a gene called CCR5 to build resistance to HIV. The virus requires the CCR5 gene to enter human blood cells.

New research has found that the same ‘edit’ also has other consequences: in one study, scientists found that it makes mice smarter, and that it could also improve brain recovery after stroke and can be linked to greater success in school.

The paper was published by researchers at the University of California, Los Angeles. Alcino J. Silva, one of the neurobiologists part of the research, told Technology Review, “The answer is likely yes, it did affect their brains.”

“The simplest interpretation is that those mutations will probably have an impact on cognitive function in the twins,” he said. Silva said it was impossible to predict the exact effect the genetic editing will have on the twins’s cognition.

“That is why it should not be done,” he said.

Chinese scientist He Jiankui. Credit: REUTERS/Stringer/File Photo

He’s experiment was widely criticised globally. The researcher is under investigation and a report by the country’s state-owned media suggested that He might have intentionally evaded oversight in a quest for “fame and fortune”.

While He may not have intended to create “smarter” babies, evidence of the link between CCR5 and cognition has been available since 2016. Silva was also part of the team that produced that evidence, showing that removing the gene from mice improved their memory significantly.

The Chinese geneticist was certainly aware of this link. On November 28, 2018, two days after news of the “gene-edited” babies became public, he was asked about the implications of the gene on the brain, citing the 2016 study.

He responded that the paper need more “independent verification”. The researcher also stated he was opposed to “genome editing for enhancement”.

The new paper found that people who naturally lack CCR5 recover more quickly from strokes. According to Technology Review, people missing at least one copy of the gene “seem to go further in school, suggesting a possible role in everyday intelligence”.

UCLA biologist S. Thomas Carmichael, who led the study, said it is the first to report a function of CCR5 in the human brain and a higher level of education. Calling the results “tantalising”, he said it needs further study.

Also Read: Is There More to Gene Editing Than Creating ‘Designer’ Humans?

The team also underlined the difference between correcting deficits in adult patients and engineering enhancements before a baby’s birth.

While these enhancements could be possible in future, the researchers said that at present, there is a lot to learn about the unintended consequences of gene-editing.

Clinical trials are already underway on stroke patients suffering memory problems. By giving them the anti-HIV drug Maraviroc, researchers are attempting to find it their cognition can be improved.

In India, ethical guidelines prevent research related to germline genetic engineering or reproductive cloning (which is what He attempted). It allows editing the genomes of adult human cells, subject to an approval from the ethics committee.

As The Wire has previously reported, Indian are editing genome cells obtained from patients, largely to develop therapies for blood disorders due to defects in single genes.

University of California’s Fresh CRISPR Patent Could Revive Gene-Editing Row

The bitter dispute between the university and the Broad Institute over patent rights for the valuable CRISPR technology was settled recently in court.

New Delhi: The University of California (UC) will soon gain its third patent on the gene-editing technology knows as CRISPR, four years after it entered into a legal battle with the Broad Institute due to a crossover between patents filed by the two parties.

UC has obtained a notice of allowance from the US Patent and Trademark Office, meaning the patent will likely be received in eight weeks.

CRISPR is a natural mechanism that prokaryotes use to defend themselves against viruses. Prokaryotes are unicellular organisms whose cells lack membranes. Eukaryotes are multicellular and their cells have membranes.

The CRISPR-Cas9 system, developed first by the University of California, combines CRISPR with Cas9 – a protein – to create a molecular tool. This tool can pick out and cut specific sections of a gene, removing it from the genetic sequence. It can be used to remove faulty genes that result in undesirable mutations.

Because of this, patent rights to the technology are likely worth millions of dollars as it can revolutionise the treatment of diseases and assist with genetically modifying crops. CRISPR-Cas9 has proved to be more efficient that other gene-editing technologies.

The new patent was awarded to UC in collaboration with Emmanuelle Charpentier of Umeå University and Krzysztof Chylinski of the University of Vienna. According to the university’s CRISPR lead patent strategist Eldora Ellison, the newer version of CRISPR is more careful about where the genetic sequence needs to be cut.

Also Read: Is There More to Gene Editing Than Creating ‘Designer’ Humans?

According to Reuters, the fresh patent stems from an application filed in 2012 by microbiologists Jennifer Doudna of the University of California at Berkeley and Charpentier.

This application was the first ever for a CRISPR-related patent. The scientists discovered that CRISPR-Cas9 could be used to edit the DNA of prokaryotic cells.

The Broad Institute, a research centre affiliated to the Massachusetts Institute of Technology (MIT) and Harvard University, also applied for their own patent that could edit the DNA of eukaryotic cells.

The team, led by bioengineer Feng Zhang, opted for a fast-track review process, which meant they landed the first CRISPR patent in 2014. The UC’s first patent was only granted in early 2018.

Because the University of California felt there was a crossover between the two patent applications, it filed a petition with the Patent and Trademark Office in 2015. It said the Broad Institute’s work was not patentably different from that of Doudna and Charpentier.

However, in late 2017, the USPTO’s Patent Trial and Appeal Board rejected the claim. The board’s decision was upheld by a federal court in September 2018. The Wire has previously reported the consequences of the court’s decision.

The fresh patent is likely to revive the rivalry between the university and the Broad Institute. UC reported that other systems and CRISPR-related patents are already under development.

However, David Cameron, spokesman for the Broad Institute, said the fresh patent “does not affect the CRISPR patent estate held by Broad, MIT and Harvard in any way”.

To exploit the lucrative nature of the technology, both institutions have licensed their intellectual property to biotech companies. Some companies are using the technology to develop treatments for sickle cells (inherited conditions that affect red blood cells), the rare blood disease beta thalassemia and other ailments.

Where do UC’s three patents differ?

Ellison, the university’s lead strategist, said the three patents are not limited to use in eukaryotes. They allow CRISPR to be used in both cellular and noncellular environments, such as laboratories.

The three patents differ in the specific guide RNAs. Guide RNAs direct the Cas9 protein in the CRISPR technology to a specific genome location to accurately edit the DNA.

While older patents were limited to research, the new one will have implications for commercial use as well.

“Together, this patent application and prior U.S. Patent Numbers 10,000,772 and 10,113,167, cover CRISPR-Cas9 methods and compositions useful as gene-editing scissors in any setting, including in vitro, as well as within live plant, animal and human cells,” the university said in a statement.

The new patent will encompass the use of CRISPR-Cas9 technology in “any cellular or non-cellular environment,” Ellison stated.

China Clones Gene-Edited Monkeys for Sleep Disorder Research

The cloned monkeys already show signs of “negative behaviour”.

Shanghai: Chinese scientists have made clones of a gene-edited macaque to aid research of circadian rhythm disorders that are linked to sleep problems, depression and Alzheimer’s disease, the official Xinhua news agency said on Thursday.

It was the first time multiple clones had been made from a gene-edited monkey for biomedical research, the agency said. The clones were born at the Institute of Neuroscience at the China Academy of Sciences in Shanghai.

A gene-edited monkey most prone to the disorder was selected as a donor, and its fibroblasts were used to make five cloned monkeys, Xinhua said, citing National Science Review, a Chinese journal.

A monkey cloned from a gene-edited macaque with circadian rhythm disorders is seen in a lab at the Institute of Neuroscience of Chinese Academy of Sciences in Shanghai, China January 18, 2019. Credit: China Daily via Reuters

The official China Daily said the clones would pave the way for more research into such problems in humans, which have become a major mental health concern.

The cloned monkeys already show signs of “negative behaviour”, including sleep disorders, as well as elevated levels of anxiety and “schizophrenia-like behaviours”, the paper added.

Xinhua said the programme, supervised by the institute’s ethics panel, was in line with international ethical standards for animal research.

Chinese Scientist Who Made Gene-Edited Babies Evaded Oversight to Seek Fame: Report

The safety and efficacy of the technologies scientist He Jiankui used are unreliable and creating gene-edited babies for reproduction is banned by national decree.

Beijing: A Chinese scientist who said he made the world’s first “gene-edited” babies intentionally evaded oversight and broke national guidelines in a quest for fame and fortune, according to a government investigation quoted in state media on Monday.

Scientist He Jiankui said in November that he used a gene-editing technology known as CRISPR-Cas9 to alter the embryonic genes of twin girls born that month, sparking an international outcry about the ethics and safety of such research.

Hundreds of Chinese and international scientists condemned He and said any application of gene editing on human embryos for reproductive purposes was unethical.

Chinese authorities also denounced He and issued a temporary halt to research activities involving the editing of human genes.

He had “deliberately evaded oversight” with the intent of creating a gene-edited baby “for the purpose of reproduction”, according to the initial findings of an investigating team set up by the Health Commission of China in southern Guangdong province, Xinhua news agency reported.

Also Read: How a Rogue Chinese Experiment Might Affect Gene-Based Therapies in India

He had raised funds himself and privately organised a team of people to carry out the procedure in order to “seek personal fame and profit,” Xinhua said, adding that he had forged ethical review papers in order to enlist volunteers for the procedure.

The safety and efficacy of the technologies He used are unreliable and creating gene-edited babies for reproduction is banned by national decree, the report said.

The case files of those involved who are suspected of committing crimes have been sent to the ministry of public security, an unnamed spokesperson for the investigation team was quoted by Xinhua as saying.

Neither he nor a representative could be reached for comment on Monday.

He defended his actions at a conference in Hong Kong in November, saying that he was “proud” of what he had done and that gene editing would help protect the girls from being infected with HIV, the virus that causes AIDS.

His announcement sparked a debate among Chinese legal scholars over which laws he had technically broken by carrying out the procedure, as well as whether he could be held criminally responsible or not.

Many scholars pointed to a 2003 guideline that bans altered human embryos from being implanted for the purpose of reproduction and says altered embryos cannot be developed for more than 14 days.

(Reuters)

How a Rogue Chinese Experiment Might Affect Gene-Based Therapies in India

Many Indian scientists edit the human genome in cells obtained from their patients.

The gene-editing tool CRISPR Cas9 became a talking point among biologists after He Jiankui, a Chinese researcher, announced he had edited the genomes of two babies in November. In a YouTube video, Jiankui explained he had cut the CCR5 gene out to make them resistant to HIV. The episode set off a furore in the international biologists community.

The genetic editing of human embryos is banned in most of the world. This is partly because scientists are still learning how to use CRISPR to do this.

“CRISPR has certainly made gene-editing easier, but the strategy is not entirely foolproof and may sometimes introduce mistakes at unintended positions” of the genome, Debojyoti Chakraborty, a scientist at the Institute of Genomics and Integrative Biology, New Delhi, told The Wire. What these off-target changes could cause remains uncharted territory.

Sonam Mehrotra, a scientist at the Advanced Centre for Treatment, Research and Education in Cancer, Mumbai, said, “From practical experience, I can tell you that the outcome of CRISPR varies between cases.” Mehrotra uses CRISPR to deliberately introduce mutations in fruit flies (Drosophila melanogaster). Given the vagaries of working with flies, whose genomes are much smaller, she thinks it’s way too early to edit human embryos.

However, both Mehrotra and Chakraborty agree CRISPR has a lot of potential to treat genetic disorders.

Also read: Editing Embryos – Six Steps to an Informed Opinion

The human genome is a long sentence composed of four alphabets: A, T, G and C. Sometimes, when a wrong alphabet appears in a given position in the sentence, it could cause a genetic disease. Armed with CRISPR, scientists are learning how they can correct these mistakes by editing the faulty part.

This is the opposite of what Jiankui did. The embryos he edited didn’t have any genetic errors that made them susceptible to HIV. Instead, Jiankui modified the sequence of letters such that the newborn twins were “ resistant to HIV,” Chakraborty explained. ‘This kind of preventive medicine is not what scientists are aiming for, especially now, while we are still trying to understand CRISPR biology.”

This rather questionable use of CRISPR has since sparked a dialogue on human gene-editing regulations.

Tinkering with genetic material is a sensitive issue because it impinges on one’s identity. At present, there is an international moratorium on the genetic editing of human embryos for reproductive purposes. The practice has even denounced by China’s medical board; it only permits the editing of human embryos less than 14 days old.

In India, the ethical guidelines of the Indian Council of Medical Research (ICMR) disallow any research related to germline genetic engineering or reproductive cloning. But editing the genomes of adult human cells is permissible subject to approval by an ethics committee.

In administrative terms, “we have three levels of regulation,” S.R Rao, senior advisor to the Department of Biotechnology, said at a talk at the second International Summit on Human Genome Editing. It was held in Hong Kong in the last week of November 2018, and counted Jiankui among its participants.

At the first level, an institutional ethical committee screens all proposed projects. The approved ones are then assessed by a risk evaluation body of the Department of Biotechnology. In cases where there could be risks to the environment, the project may require an ‘okay’ from the environment ministry as well.

All clinical trials involving genetic engineering products come under the Drugs and Cosmetics Act, 1940.

Thus far, this labyrinthine process has not deterred scientists from exploring CRISPR as a treatment option for genetic disorders. Many Indian scientists edit the human genome in cells obtained from their patients. Their biggest focus area is developing a therapy for blood disorders due to defects in single genes.

This form of genetic editing is distinct from embryonic editing because it involves adult patient cells, not germ cells. The problem with editing the DNA of embryos is that both somatic and germ cells will carry the mutation, and the edited DNA will be passed on hereditarily.

But when working with adult cells – such as blood cells from patients – CRISPR can be used to correct mutations in the lab. And since the technique is patient-specific, any alterations made in the genome remain confined to one individual and won’t affect the next generation.

In that sense, CRISPR presents a lot of opportunities. China realised this early and eased regulations. And so far, Chinese scientists have used CRISPR to edit the genes of monkeys, human embryos less than 14 days old and are currently testing CRISPR-based therapies in cancer patients.

Things are moving in the US as well. American scientists having embarked on CRISPR-related clinical trials, with the country’s Food and Drug Administration keeping a close watch.

India is yet to start.

At the moment, scientists like Chakraborty are testing proof-of-concept studies in the lab, where he and his colleagues attempt to correct mutations in human blood cells. The next step is to test the technique in animal models, and then begin human trials. The timeline hasn’t been finalised, however.

“Technically, genome editing is not a challenge,” Chakraborty said. But one of CRISPR’s bigger caveats is that one size doesn’t fit all. “The outcome of CRISPR-based therapies will differ from one cell to another, from one gene to another and even from one delivery agent to another,” Chakraborty said. So each clinical trial will have to seek approval on a case-by-case basis. This does suggest officials will pay each proposal the attention it deserves – but it still also falls short.

Also read: Is There More to Gene Editing Than Creating ‘Designer’ Humans?

What India really needs, and lacks at the moment, is a proper framework to regulate CRISPR-based clinical trials. There has been a lot of talk about the need for new policies “but India is unlikely to go the China way in hurrying things up,” Deepti Trivedi, a scientific officer at the National Centre for Biological Sciences, Bengaluru, told The Wire.

Mehrotra is particularly worried about how Jiankui’s brazen foot forward may affect the future of CRISPR Cas9. “If a handful of researchers continue these reckless acts, governments may impose stringent regulations on the use of CRISPR.” This has already happened with stem cells: fearing rampant malpractice, the ICMR banned the use of stem cell technology in 2017 and limited access to them.

Jiankui’s actions prompted a sharp response from the Chinese government. It launched an investigation into his work, his university suspended him and he might be under house arrest. At the same time, scientists rallied to plan a gene-editing meeting in Massachusetts this year, where social scientists and geneticists will discuss the technology’s central issues.

Notwithstanding whether Indian scientists are going to be part of this conversation, Chakraborty believes something similar – “a dialogue between scientists and policymakers” – needs to happen in India. If it doesn’t, this path-breaking tech might never leave the pharmaceutical fringes it currently occupies.

Sarah Iqbal is a freelance science writer.

Should GM Crops Feature in the ‘Evergreen Revolution’ India Dearly Needs?

K. VijayRaghavan, principal scientific adviser to the Government of India, and M.S. Swaminathan discuss an article the latter recently penned arguing that GM crops are unsustainable in the prevailing regulatory regime.

In November, M.S. Swaminathan and P.C. Kesavan penned an article in the journal Current Science criticising genetically modified organisms (GMOs). The text polarised readers, drawing widespread support as well as criticism.

Kesavan and Swaminathan began by asserting the need for an ‘Evergreen Revolution’ to improve agricultural productivity and sustainability without the “adverse environmental and social impacts” of the Green Revolution.

They then argue that Bt crops and herbicide-tolerant crops cannot be part of this regime because they are “highly unsustainable”. They conclude asking for more basic research to “understand the causes of ‘unintended effects’” and that it would be “prudent to adhere to the recommendations of the Task Force on Agricultural Biotechnology … (2004)” when developing GM crops.

In a recent email exchange, K. VijayRaghavan, principal scientific adviser to the Government of India, debated the article’s points with Swaminathan. The emails were placed in the public domain (available to read here). The following excerpt reproduces the last emails from each scientist, with their consent. They are presented in full, lightly edited for style.

Dear Prof VijayRaghavan,

An article by Prof Kesavan and me in Current Science seems to have caused considerable concern and confusion. The last para of the article reads as follows:

Genetic engineering technology has opened up new avenues of molecular breeding. However, their potential undesirable impacts will have to be kept in view. What is important is not to condemn or praise any technology, but choose the one which can take us to the desired goal sustainably, safely and economically.

As far as I am concerned, the following has been my view throughout.

It is unfortunate if the article has created the impression that I am opposed to GM as a technology. Technology always creates divergent viewpoints. For example, the gene-editing technology CRISPR is now undergoing divergent views. This is why it is important to have a transparent regulatory mechanism which is supported by professionals, government departments and the private sector. I shall be grateful for your views on how to clarify our views on biotechnology. After all we started genetic engineering research in 1990 for transferring genes from mangroves to rice for salt tolerance.

Genetic modification is the technology of choice for solving abiotic problems like drought flood, salinity, etc. It may not be equally effective in the case of biotic stresses since new strains of pests and diseases arise all the time. This is why the [M.S. Swaminathan Research Foundation] choose mangroves for providing genes for tolerance to salinity.

I have always said that the green revolution should not become a ‘greed revolution’ and therefore we should ensure that the long-term productivity of the soil and water also becomes a part of the technology. I also believe that GMO is the best pathway for breeding crop varieties with resistance to abiotic stress and will hence become more important in an era of climate change.

I thought I should let you know that there has been some misunderstanding about my views to ensure sustainable productivity by avoiding the spread of greed revolution resulting in the undermining of the long term production potential. In this context, Norman Borlaug and I shared the same concern for ensuring sustainable food and nutrition security.

I hope you are all well. I send you and your family my good wishes for your health and happiness during the Christmas and New Year.

With warm personal regards,

Yours sincerely,

M.S. Swaminathan

Also read: Why Genetic Engineering is Stranger Than You Think it is

K. VijayRaghavan responds

Dear Professor Swaminathan

Many thanks for your e-mail. I am very glad that you took the time to reach out and explain the recent Kesavan and Swaminathan ‘review’ in Current Science. I am also pleased to hear your clarifications and views on new technologies in agriculture. As requested by you in your mail, may I respectfully submit my very serious concerns about the review?

In your e-mail, you highlight the last paragraph of the review:

Genetic engineering technology has opened up new avenues of molecular breeding. However, their potential undesirable impacts will have to be kept in view. What is important is not to condemn or praise any technology, but choose the one which can take us to the desired goal sustainably, safely and economically.

Yet, as scientists, we must read and understand the article as a whole and not look at it selectively. We then distill its key messages. A review article in science usually analyses the literature, presenting multiple examples in an area. It then summarises the state of the field. Next, it summarises the consensus in the field and then gives the view of the authors, stating why they agree or disagree. The Kesavan and Swaminathan piece is more of an opinion piece than such a review. But that is a quibble.

Whatever the nature of the piece, there is a requirement that that any article:

a. Not selectively omit inconvenient results

b. Not selectively represent work that suits one’s hypotheses as valid without referring to the other work that discredits it and explaining the rationale for the choice made

c. Not misrepresent referenced work. That is, if the work says one thing but the article (the review in this case) refers to it as saying the opposite or something very different.

The Kesavan and Swaminathan review starts by pointing out how fertilisers, pesticides, high-yielding varieties of crops, etc. ushered major changes in agriculture but also raised major concerns for sustainability and ecology. One cannot but agree with such a generalisation. (Similarly, it can be argued that extensive mining, the steam locomotive, the internal combustion engine, an addictive use of fossil fuels, greenhouse gas emissions, a huge livestock population, air-travel, shipping, the chain-saw, ocean trawlers, etc. have contributed to pushing our planet to the edge. One cannot but agree with such generalisations, too).

Thus, in this part of the article, while pointing out important concerns of intensive agriculture, the review neglects to put this in the context of broader issues of human intervention. In that – in this part – it can charitably be said to have merely missed an opportunity.

But the review uses the above to make a case for how the unintended consequences of technologies per se can have a negative impact. Here, it omits … the distinction between the technologies and the nature and extent of their use by human agencies. These consequences of technologies are then used to segue into views on GM crops, the main thrust of the review: arguing that one must be wary of technologies in general.

In this section on GM, sadly, the review is even more severely flawed. The specific instances where results are selectively omitted, selectively represented or misrepresented are rife. Each of these egregious [instances], I am sure, will be addressed in response to your review by scientists soon. Indeed, the bulk of the scientific points made in this part of the review have been raised previously and have been scientifically discredited widely and one has to only study the literature to see this.

The review puts in one bin the four components of efficacy, safety, commercial interests and regulation. And, above this, the review seamlessly flows from one type of genetic modification to another, clubbing them all together. This is not only flawed scientifically [but] has the implication that those who defend the science or the regulatory system are defending specific commercial interests or loss of biodiversity.

Finally, the review makes extraordinary generalisations about the Indian regulatory system. It alleges both incompetence and collusion. These are very, very serious allegations against entire committees and the Government of India. (It is this same structure, incidentally, which has put in place and monitors the regulation of GM research at the MSSRF, which your letter refers to.) In a complex area that involves many fields, India’s regulatory system has steadily ratcheted its quality over the years. It acts in accordance with national law, international protocols and best-in-class procedures.

Critical analysis and criticism are always welcome. But gratuitous generalisations undermine years of work and, more importantly, cause deep and lasting damage to entire areas of research and consequently to our people at large.

The use of GM technology and its release in agriculture is and must be regulated and done well. Experts, as also the authors, know that there are many kinds of such GM technologies. Some involve loss-of-function, others involve gain-of -function, yet others involve new function. There is research and development in the publicly funded sector and in the private sector the world over. There are commercial interests and public interest, which may overlap in one case and not in another.

There are vested interests in all parts of the spectrum and there are also very genuine people across the spectrum. There are environmental and biodiversity issues which may be very critical in some cases and less so in another. There are new technologies, which may require new regulatory steps.

In these and in all matters, we as scientists are obliged to take a careful and rational view. Evidence must always be critically examined and expressed with neither fear nor favour in our research work and in the opinions and advice we publicly, privately and officially give. We must have the courage to change our views when presented with new contrary evidence.

What needs to be done with the evidence, in terms of process, policy or action, is another complex area that involves interacting with society, and dealing with reality and perceptions, with real and imagined concerns, economics, etc. This is also a difficult task and scientists have a critical role here, too.

Also read: Why Transgenic Mustard is Unlikely to Hurt You or Your Environment

Today’s world is at a tipping point. In the Anthropocene epoch, humans are the stewards of the planet’s future. Difficult local and global decisions have to be taken by the peoples of the world. For this, the public must have access to the complexities of every debate, conveyed by scientists in their writings and talks. Neither the hubris of technologies nor the blanket denial of their roles makes sense.

Eminent scientists and global leaders, such as you, have participated and coordinated discussions on these issues. Their voice [has] a special impact in society. Their missteps also have consequences that are immense, sometimes very damaging and lasting. In a large country like ours, the damage can be vast and deep.

I have been frank and critical because, quite simply, I would be negligent if I were otherwise. We stand by the entirety, not selective parts, of our publications and are free to revise our views or not. Your mail points out some aspects that you particularly stress. I must presume that you nevertheless continue to stand by the entirety of the publication. In any event, with the Kesavan and Swaminathan opinions in public, I am sure that various protagonists will publicly respond and discuss, which is what should be done in science.

I deeply admire and applaud your many contributions to science, your wisdom and your courage and your national and international contributions. We all look forward to your continued role in science and in policy.

With warmest personal regards,

K. VijayRaghavan, Principal Scientific Adviser, Govt. of India
MSS/DB/7 December 2018

China’s Scientific Community Confronts ‘Rogue Science’

Fears are growing in China over the lack of oversight and transparency for major weather modification projects in Tibet and other boundary-pushing projects.

November began with Chinese scientists advancing the world’s largest weather modification project and ended with a Chinese researcher’s claim to have produced the first gene-edited babies. Both of these futuristic announcements were met with a fierce backlash in China. Over 100 scientists signed a statement criticising the gene-editing experiment for sacrificing ethics in the blind pursuit of progress. Meanwhile, a group of meteorologists publicly questioned the government’s investment in “Sky River”, a sweeping artificial rain project that remains theoretical.

These rare outcries from China’s scientific community have exposed flaws in the governance of cutting-edge scientific experiments, which loom large as the country looks to science and technology breakthroughs to address its environmental and social challenges.

Diverting water in the sky

The root of the Chinese character “to govern” (治) is water. For rulers over the centuries, controlling floods in the southern Yangtze River Basin and managing drought in the northern Yellow River Basin has long been central to political legitimacy and stability in China. With climate change projected to increase the intensity of droughts throughout China and widen drought-affected areas in the north-west, among other regions, Chinese scientists have faced greater pressure to manage water supplies.

Through the South-North Water Diversion project, first envisioned by Mao Zedong in the 1950s, the Chinese government has built two major canals channelling an additional 27.8 billion cubic metres of water north every year (about 3% of the Yangtze’s annual discharge volume). However, a third route, which would divert water from the Yangtze’s tributaries to the Yellow River at their headwaters on the Qinghai-Tibetan Plateau has stalled due to engineering challenges.

To avoid the hassle of moving water on land, scientists have looked to the sky for inspiration. The “Sky River” project is considered part of the third route, except the water transfer would happen in the atmosphere, rather than through canals.

Also read: The Modi Government’s Pseudoscience Drive Is More Than an Attack on Science

Back in the early 1990s, MIT scientists used the concept of “atmospheric rivers” to describe water vapour transport bands they identified in the troposphere. China’s Sky River project proposes large-scale manipulation of these bands of water vapour using cloud-seeding techniques that could manufacture rainfall.

According to Wang Guangqian, president of Qinghai University and the leader of the Sky River team, the project seeks to increase rainfall at the headwaters of the Yangtze and Yellow rivers where “cloud resources are abundant”. Without intervention, these weather systems would typically move to the southern Yangtze basin where rainfall would naturally occur. By cutting off the migration of rain clouds in the Qinghai-Tibetan plateau using cloud-seeding, the team hypothesises they could supplement the flow of the northern Yellow River.

The Qinghai-Tibetan plateau could get more rainfall under the proposed Sky River project. Credit: Pixabay/lijia970329

Manufacturing rain

In 2015, Tsinghua University, Qinghai University, and the province’s meteorological bureau set the Sky River project in motion, forming a research partnership, according to ScienceNet.

Sky River quickly gained political support: it was featured in Qinghai province’s 13th Five-Year Plan and received 53 million yuan (USD 7.7 million) of funding from the provincial government and Qinghai University. Tsinghua also committed one million yuan (USD 145,000) a year.

The project also received national level funding and support. In 2016, the Ministry of Science and Technology accepted the project as a “technological innovation project with international significance”. Subsequently, it was designated a national key research project, according to Wang Guangqian.

The team has been experimenting with techniques to seed clouds over large geographies. One method uses chambers that burn and send silver iodide particles into the atmosphere to seed clouds. One of the project’s researchers told the South China Morning Post, “[So far] more than 500 burners have been deployed on alpine slopes in Tibet, Xinjiang, and other areas for experimental use.” The researcher described how “sometimes snow would start falling almost immediately after we ignited the chamber. It was like standing on the stage of a magic show.” The project intends to build tens of thousands of these chambers.

Also Read: China’s Belt and Road Initiative Will Make or Break Global Climate Fight

Backlash from the science community

China has engaged in localised cloud-seeding for over 50 years, but implementing such an extensive project would be an unprecedented intervention. According to plans released in 2016, the project hopes to increase rainfall in the medium- to long-term by five billion cubic metres – nearly one fifth of the water transferred through the existent South-North canals. In the 13^th Five-Year Plan period alone, the team plans to boost rainfall in the Sanjiangyuan region of the Tibetan plateau by half that amount. Wu Guoxiong, an atmospheric scientist at the Chinese Academy of Sciences, doubts that it is possible to reach those levels of artificial rainfall: “Artificial rain is still in the experimentation phase, so far the best results have increased rainfall by 10-20%.”

Criticism escalated last month when China’s Aerospace Science and Technology Corporation announced that it was developing monitoring satellites and rockets to aid the Sky River project. The company said they would launch two satellites by 2020 and complete a network of six by 2022.

Scientists lambasted the high-profile technology investment. Lu Hancheng, a professor at the National University of Defense Technology’s Institute of Meteorology and Oceanography, told ScienceNet, “This is an absurd fantasy project with neither scientific foundation nor technical feasibility. That it got support to launch is incomprehensible. Public funds should be cherished.” Other experts commented that meteorologists, who they say have not been included so far, should have been consulted.

In an interview with China.com Wang Guangqian, emphasised that the project is still at an early stage. He also said the project has gone through serious review with meteorologists involved. Government funding has been spent judiciously, he maintained, saying that the satellites would be used for other purposes beyond the Sky River project.

Governance scheme needed

The project may be far from operating at full-scale; however, critics say China’s scientific experimentation can rapidly escalate from concept to implementation without proper safeguards. This was the case with the recent gene-editing experiment. The scientist did not submit his work for peer review or file the experiment as a clinical trial with the government before implanting genetically modified embryos in real human subjects, a step that scientists globally have considered out of bounds.

The gene-editing experiment was undertaken by a biophysicist without experience in human clinical trials. Similarly, the Sky River team has been criticised for being composed primarily of hydrologists, not meteorologists.

Beyond the importance of a project’s scientific basis, Chen Ying, a senior research fellow on the governance of geoengineering at Chinese Academy of Social Sciences, said that projects also need to be reviewed more holistically. She said that Wang Guangqian, the Sky River project leader, has focused on water resources without considering governance issues. “Technology is the foundation, but even if the technology is feasible, it doesn’t mean the project should be carried out. You need to comprehensively and objectively evaluate economic, ecological, ethical and other effects,” she said.

Cross-border impacts?

Experts interviewed by chinadialogue said that the risks involved in the Sky River project remain unclear due to insufficient research. The cloud-seeding chambers in use are reportedly clean enough to operate in conservation areas, but they emit carbon dioxide. The larger effects of altering the region’s climate are not well-documented, but the project could affect local and transnational ecosystems given it will take place at the source region of Asia’s major rivers.

Both Chen Ying and John Moore, a British scientist at Beijing Normal University who leads China’s national geoengineering research, said that unlike past small-scale cloud seeding, the Sky River project could be considered a form of large-scale geoengineering, the alteration of natural systems to fight climate change. “If the full-scale project were shown to be feasible and could achieve what they want, I would say it’s climate engineering. But I am highly sceptical that it is at all feasible from a scientific perspective,” said Moore.

Also Read: What India Can Learn From China’s Environment Protection Reforms

Geoengineering scientists understand the risks and would not rush into outdoor experimentation, Chen Ying said, but it is necessary to remain alert to scientists who don’t understand geoengineering inadvertently pursuing similar experimentation. Governance mechanisms are required in order to avoid this, she said.

Researchers at Oxford University proposed a set of global principles governing geoengineering, including public participation, independent assessment of impact, and most importantly, “governance before deployment”. However, these have yet to be adopted as international law. The only international rule that exists is a guideline for geoengineering field experimentation established under the UN Conference for Biological Diversity (CBD). The guidance permits small-scale field studies “subject to a thorough prior assessment of the potential impacts on the environment”. China, as a party to the CBD, is held to this guideline.

Theory into practice

One outcome of the recent controversies is that the Chinese and international scientific communities have become more outspoken. Already, public pressure has had an effect. He Jiankui, the scientist behind the gene-edited babies, is under investigation and China’s vice minister of science and technology said his scientific activities would be suspended. As for the Sky River project, after the meteorologists’ criticisms, it has taken a step toward greater transparency. Wang Guangqian said that the public is welcome to visit the project’s Qinghai lab.

From the spread of diseases to adapting to climate change, scientists will come under increasing pressure in the 21^st century to push the boundaries of their fields, inevitably straining existing governance mechanisms. In his interview, the Sky River project leader reflected the impulse to act saying, “We don’t want to just publish theoretical papers, we want to apply our papers to the earth”.

Lili Pike is a researcher for chinadialogue and the executive producer of the Beijing Energy Network’s podcast, Environment China.

This article was originally published on The Third Pole. Read the original article here.

Creation of Designer Babies Is Limited by Biology, Not Technology

Forecasts of designer babies followed the announcement of the gene-edited twins, just as they have for any reproductive technology since 1978. This signals the public must learn more about genetics.

When Adam Nash was still an embryo, living in a dish in the lab, scientists tested his DNA to make sure it was free of Fanconi anemia, the rare inherited blood disease from which his sister Molly suffered. They also checked his DNA for a marker that would reveal whether he shared the same tissue type. Molly needed a donor match for stem cell therapy, and her parents were determined to find one. Adam was conceived so the stem cells in his umbilical cord could be the lifesaving treatment for his sister.

Adam Nash is considered to be the first designer baby, born in 2000 using in vitro fertilisaton with pre-implantation genetic diagnosis, a technique used to choose desired characteristics. The media covered the story with empathy for the parents’ motives but not without reminding the reader that “eye colour, athletic ability, beauty, intelligence, height, stopping a propensity towards obesity, guaranteeing freedom from certain mental and physical illnesses, all of these could in the future be available to parents deciding to have a designer baby.”

The designer babies have thus been called the “future-we-should-not-want” for each new reproductive technology or intervention. But the babies never came and are nowhere close. I am not surprised.

I study the prediction of complex diseases and human traits that result from interactions between multiple genes and lifestyle factors. This research shows that geneticists cannot read the genetic code and know who will be above average in intelligence and athleticism. Such traits and diseases that result from multiple genes and lifestyle factors cannot be predicted using just DNA, and cannot be designed. Not now. And very unlikely ever.

Designer babies are next

The inevitable rise of designer babies was proclaimed in 1978 after the birth of Louise Brown, the first IVF baby, as the next step toward “a brave world where parents can select their child’s gender and traits.” The same situation occurred in 1994 when a 59-year-old British woman stretched the limits of nature by giving birth to twins using donated eggs that were implanted in her womb at a fertility clinic in Italy.

The response was the same in 1999, when a fertility clinic in Fairfax, Virginia, offered sex selection of embryos to screen against diseases that only happen in boys. In 2013, when 23andMe was granted a patent for a tool that predicts the likelihood of traits in babies based on DNA of two parents, the question of patenting designer babies was raised. In 2016, when the UK permitted a woman to donate her healthy mitochondria to a couple using IVF to conceive a child, raising the number of parents to three, fears of unnatural children rose again. Last month, when Genomic Prediction, a New Jersey company, announced its DNA screening panel for embryos would also assess the risk for complex diseases such as Type 2 diabetes and heart disease that are caused by multiple genes, fears of engineering babies with high IQ or athletic prowess emerged.

Also read: Chinese Scientist Claims to Have Helped Make World’s First Gene-Edited Babies

The same issues arose on November 26 when He Jiankui reported at the Second International Summit on Human Genome Editing in Hong Kong that he had successfully edited the DNA of twin baby girls born last month.

The designer baby doom scenarios have not evolved with the technology. It’s been the same story for decades. It’s the same “desirable” traits and the same assumption that parents want to select these traits if technology allowed. But no one seems to be questioning whether these traits are solely a product of our genes such that they can be selected or edited in embryos.

Wondering about designer babies was understandable in the early days, but a repetition of these supposed fears now suggests lack of understanding of how DNA, and the genes they encode, work.

Designing favourable traits in babies is not simple

Although there are exceptions, DNA generally differs between people in two ways: There are DNA mutations and DNA variations.

Mutations cause rare diseases like Huntington’s disease and cystic fibrosis, which are caused by a single gene. Mutations in the BRCA genes substantially increase the risk of breast and ovarian cancer. Selecting embryos that do not have these mutations removes the entire or main cause of disease – women who don’t have BRCA mutations can still develop breast cancer through other causes, like all women.

Variations are changes in the genetic code that are more common than mutations and associated with common traits and diseases. DNA variants increase the likelihood that you may have a trait or develop a disease but do not determine or cause it. Association means that in several large study populations, a DNA variant was more frequent among people with the trait than those without, often only slightly more frequent.

These variants don’t determine a trait, but increase its likelihood by interacting with other DNA variants and nongenetic influences such as upbringing, lifestyle and environment. To design such traits in embryos would require multiple DNA changes in multiple genes and orchestrating or controlling relevant environment and lifestyle influences too.

Let’s compare it to driving a car. DNA mutations are like the flat tires and the failing brakes: technical problems that make driving problematic, no matter where you drive. DNA variations are like the colour and the type of car, or other features of the car that may affect the driving experience and even might create problems over time. For example, a convertible is a delight when driving on Hollywood’s Sunset Boulevard on a breezy summer evening, but cruel when crossing a high mountain pass in midwinter. Whether features of the car are an asset or a liability depends on the context and that context might change – they are never ideal all the time.

Also read: All You Need to Know: The Latest Gene Editing Breakthrough

Another hurdle

Most DNA mutations do nothing else other than cause the disease, but DNA variations may play a role in many diseases and traits. Take variations in the MC1R “red hair” gene, which not only increases the chance that your child will have red hair, but also increases their risk of skin cancer. Or variations in the OCA2 and HERC2 “eye colour” genes that are also associated with the risk of various cancers, Parkinson’s and Alzheimer’s disease. To be sure, these are statistical associations, reported in the scientific literature, some may be confirmed; others may not. But the message is clear: Editing DNA variations for “desirable” traits may have adverse consequences, including many that scientists don’t know about yet.

We can see this in the analysis of He Jiankui’s gene-edited babies. By trying to make the babies resistant to HIV, He might have greatly increased susceptibility to infections by West Nile virus or influenza.

To be sure, even though complex traits such as intelligence, athletics and musicality cannot be selected or designed, there will be opportunists who will try to offer these traits, even if totally premature and unsupported by science. Like Stephen Hsu, the co-founder of Genomic Prediction who said about his offer to test embryos for polygenic risk, the risk of a disease based on multiple genes, “I think people are going to demand that. If we don’t do it, some other company will.” And also He said: “There will be someone, somewhere, who is doing this. If it’s not me, it’s someone else.” People need to be protected against this irresponsible and unethical use of DNA testing and editing.

Science brought incredible progress in reproductive technology but didn’t bring designer babies one step closer. The creation of designer babies is not limited by technology, but by biology: The origins of common traits and diseases are too complex and intertwined to modify the DNA without introducing unwanted effects.

A Cecile JW Janssens is a Research Professor of Epidemiology at Emory University.

This article is republished from The Conversation under a Creative Commons license. Read the original article.