When she arrived at the university, this predilection turned into a career. It was at this point that she discovered a field called feedback control theory: the study of how complex systems regulate. "Everything has just been concentrated," says El-Samad, who has become systems biologist at San Francisco UC. "There is a system of checks and balances that ensures that the craziest of us are put back in order, and this is true of human societies, ecosystems and organizations. Sometimes these systems fail. And you get the war. Or sickness. "
She started building robots and designing feedback control algorithms to stabilize their movements. A few years later, while a PhD student in Ames, Iowa, she was working on automated flight control systems for Rockwell Collins, a US military aerospace subcontractor. But El-Samad worried that her job would end up in war zones like the one she grew up in. That's when she chose to design circuits for living cells.
She was not alone. In the early 2000s, many electrical engineers and control theorists joined the new field of synthetic biologythinking they could design biological circuits to control the flow of information in a cell, just as physical versions moved electrons computer chips. They began to design novel DNA chains in nature and to integrate these synthetic operating systems into bacteria and yeast. But these tools have remained blunted. Of course, you could do a drug rash against malaria E. coli, but you could not tell him to stop making the medicine when there was too much, or to make a certain amount every day at the same time. For this you need a comment check.
"There is a system of checks and balances that ensures that the craziest of us are put back in order, which is true in human societies, ecosystems and organisms."
-Hana El-Samad, UC San Francisco
And that's where El-Samad comes in, with the ideas of a Russian-American engineer named Nicolas Minorsky. You can thank Minorsky every time you press cruise control to save your car's calf, or relax in a cool, but not cold, home that's right for your Nest. In the 1920s, his penchant for computation combined with patient observations of helmsmen leading American battleships allowed Minorisky to understand the mathematical theory behind proportional-integral-derivative control, or PID. Today, PID algorithms are ubiquitous in the modern world. they run aircraft autopilot programs, keeps the robots manufacturing crush their fellow humansand do smart thermostatsgood, smart.
This week, El-Samad and a team of collaborators from David Baker's lab at the University of Washington announced that they had found a way to create a biological equivalent of a PID algorithm. It starts with a designer protein – they call it LOCKR, an abbreviation for locking orthogonal cage key pRoteins. In the form of a cage with a door locked on one side, the LOCKR opens wide when it comes into contact with a predefined molecule, revealing the hidden functions of the researchers inside the cage.
For example, in a version, this function is a tag that condemns everything attached to a pile of cellular waste. Suppose you have an enzyme that breaks down molecule A into molecules B and C. But you are afraid of ending up with too much molecule C, which can be toxic. You design a LOCKR whose key is molecule C and you merge it with molecule A. As the enzyme manufactures more and more molecule C, it opens up more of these LOCKR proteins, revealing a label for the drug. send, with the molecule A in the trash. Dump Without the molecule A, the enzyme slows down its production of molecules B and C. And that, my friends, is a feedback circuit.
Network a few LOCKR-related molecules, and you get a circuit that can control the functions of a cell in the same way as a PID computer program that automatically adjusts the height of an aircraft. With the right touch, you can shine or burst your cells. You can send items to the trash of the cell or zoom them to another cell postcode. That's what scientists showed LOCKR could do in yeast. Their long-term goal is to use LOCKR and other small synthetic molecules to program human cells so that they head themselves to diseased tissues, including the hard-to-reach brain, and that they reliably deposit a precise drug load.
Other pioneers of synthetic biology have been impressed by this breakthrough. "This technology is pretty cool," says Tim Lu, a computer biologist at MIT and co-founder of Synlogic, a company that reprograms bacteria for cancer. It has the potential to offer faster feedback control than other approaches, he says. But there is still a lot of work to be done before starting to think about integrating LOCKR with those involved: "One of the key things to evaluate for the future is potential immunogenicity."
This is El-Samad's to-do list – to determine if LOCKRs trigger a person's immune system before they can do what they are supposed to do. His team will have to study these cells for several months, if not years, to see if they are able to detect the hidden control codes and rebel against them.
If they can, human cells will not be able to administer drugs consistently, and this is a major goal. El-Samad has an important contract (she will not say what size) of Darpa, the Pentagon's moonshot division, to learn to link several LOCKRs in the hope of treating a traumatic brain injury – one of the wounds the most common among soldiers. . El-Samad and Wendell Lim, biophysics chemist at UCSF, charge synthetic circuits in white blood cells that they have designed to target the brain. Such cells produce inflammatory and anti-inflammatory molecules; The trick is to find the right mix. Not enough, and the brain can not begin to heal. Too much and they can kill neurons, resulting in behavioral changes, compromised motor skills and cognitive decline. The circuits designed by El-Samad will place the genes that produce these molecules under the control of LOCKR, in order to balance them. His team plans to begin testing on mice over the next year.
It turns out that you do not need rationally designed circuits to burst biobes on biofuels, makeup and medications. You can simply move large pieces of DNA from one organism to another and qualify it as good. What if you lose some yeast en route? Living cell therapies have changed all that, says El-Samad, referring to the increasing number of cancer treatments approved by the FDA which involve the engineering of white blood cells to detect tumors. These treatments can be miraculous, but they are also unpredictable. Sometimes T cells go to sea, secreting cytokine storms that have killed patients. Subjecting these cells to tighter control must be a priority if they want to be the future of medicine, she says.
"In the last 10 years, synthetic biology has been a very exciting field but one that really lacked meaning," adds El-Samad. Now, synthetic cell biologists must be "reliable, intelligent, and rational. Because if patients die, that's the end. So, suddenly, I think synthetic biology has regained its reason for being. "
. (tagsToTranslate) Biology (t) Synthetic biology (t) yeast (t) protein (t) genetic engineering</pre></pre>
You did not get them because 23andMe, like most other direct-to-consumer DNA companies, unravel your genetic secrets with the help of a relatively inexpensive technology called genotyping. Instead of sequencing the 6.4 billion base pairs of DNA, it takes strategic snapshots at a few hundred thousand locations in the genome, examining the different parts, important and modifiable. But as scientists frequently discover new links between DNA and disease, genes and geographiesand base pairs and behaviors, 23andMe constantly modifies the silicon wafer chips used to capture all these DNA extracts. More recently, you were in the tube and bought your 23andMe test-it was a bestseller the first day, your test is up to date. Which means that, as many 23andMe users discover, it is not always profitable to adopt early.
23andMe does not manufacture these chips, also known as arrays, but buys them at a genetic material company called Illumina. Each point of a Illumina chip saves a particular variant, a place where the DNA of a person is different from that of another person. The more you want to measure variants, the more complex and therefore expensive the chip. Think of it as the upgrade of your laptop; it probably costs more, but it's probably faster and it's colder, too. "One of the reasons for this evolution of genotyping matrices is the desire to be more efficient in terms of the number of variants measured," says Sarah Nelson, biostatistician at the University of Washington, who is studying genetic technologies.
These gains in efficiency and complexity are interesting for science, but not for genetic societies facing consumers. People inherit their genomes in chunks, not gene by gene, which allowed chip designers to find predictable relationships between variants close to each other on a given chromosome. Create a chip that captures information about specific variants spread across different chromosomes and also get information about neighboring variants at no extra cost. This is what is called imputation. "It's good for research," says Nelson, "but you can not really use imputation for variations in health reporting." If you're communicating to a person information about a rare variant which increases your risk of illness, you want it measured directly. "
That's the position of the federal government too. In late 2013, the Food and Drug Administration told 23andMe that she could no longer offer health information, at least not until society made some changesincluding ensuring that all reports on client susceptibility to the disease are based on clinically validated variants. These are small genetic differences with good evidence of their influence on people's health. To get more of these variants on a chip, 23andMe had to be upgraded.
In April 2017, the company started selling new customers. his FDA-approved health reports for things like Alzheimer's, Parkinson's disease and breast cancer. But the new rules and the new chip prevented customers who had already tested on earlier versions from doing so. The old technology was not enough to read these parts of their genome, and the policy did not give the company enough leeway to do it.
Hundreds of 23andMe customers tested on these earlier chips have pleaded with the company to get a way to access its latest features, such as health reports and improved ancestry estimates. Many worried about whether their old data was accurate. And an application for public registration of WIRED revealed that some customers had filed misleading advertising complaints with the Federal Trade Commission. For nearly a year, the company has advised all these customers to wait. A future chip upgrade policy, promised by 23andMe, would give them access to all of its services. The old spit of old customers would be used with the new chips.
But all those who salivated at the prospect of new genetic knowledge were disappointed. In an email last month, 23 and I announced that users of smart versions one, two or three should earn more money. Access to the latest ancestry reports from the company will cost $ 69; the experience more healthy ancestry will run $ 125. This is of course the first time, between $ 1,000 in 2007 and $ 99 in 2013. They will have to send more messages and wait three to five weeks to be retested on the last chip. But unlike simply acquiring a brand new kit (which would require the setup of a new profile), the upgrade process allows customers to merge their old chip data with the new items.
"Customers using the V3 smart version who have not been receiving 23andMe reports for some time, these customers have asked for a way to upgrade their 23andMe reports at a reduced cost, and this upgrade policy responds to this. ", sent a spokesman for 23andMe in response to WIRED's questions about the upgrade policy. I've noticed that the upgrade should not affect the accuracy or validity of reports generated on older chip versions. "In rare cases," he wrote, "the results may change and we will answer any questions from clients in these cases, if any."
Upgrading chips also has far more serious consequences than asking customers to spend more money. Whenever a company like 23andMe changes tables, it also has an impact on genealogical databases, and more and more about the law enforcement agencies that use them catch criminals. Web sites such as GEDmatch rely on the ability to compare the same DNA fragments between people uploading their results from different genetic testing companies to generate parent matches. The new chip used by 23andMe (and recently adopted by FamilyTreeDNa and MyHeritage) has very little overlap with older versions of chips – about 160,000 out of 630,000 variants – making the comparison more delicate and more prone to errors.
Imputation software can help upstream compatibility, says Debbie Kennett, a genealogist based in the UK. However, these algorithms are like a black box. "It's hard to judge the magnitude of the impact," she says. Third party tools, as well as the people who use them, have abundant knowledge and data produced by test companies such as 23andMe can change at any time.
Upgrading the policy or not, testing is not always possible, people without leaving saliva on the ice for their parents curious about genealogy. This means that even though 23andMe says that it does not have a schedule for future chip upgrades, the new discoveries will continue to make the existing bays obsolete. And with companies that are starting to offer complete genome sequencing for less than $ 1000, the long-term value of genotyping could prove to be such a thing. 23andMe declined to say how many of its more than 10 million customers are eligible to participate in the chip upgrade program or how many have already done so. But as DNA testing becomes more popular and more affordable, this episode is a useful reminder that these tests are consumer products and that, like phones and laptops, they are constantly evolving. Your genetic code may not change, but what you know about it will always be.
. (tagToTranslate) genetics (t) 23andMe (t) health (t) ancestry</pre></pre>
The decision, made late Friday morning, is a major victory for a new type of genetic detective work based on the results of the spindle kit genealogy-parents curious.
The case of Snohomish County was discovered when investigators collaborated with a private company to find sperm left on one of the crime scenes until Talbott through two cousins who had downloaded their own genetic information about public database called GEDMatch. These sites help people build family trees and trace their ancestral roots through a common DNA, a practice known as genetic genealogy. Recently, police departments and the FBI started using the method to unearth suspects. Genetic genealogy has already been used to advance cold cases since it has publicly culminated in the arrest of the suspect. Golden State Killer last April. But until the Talbott case was decided early this month, the technique had never been tested in court.
The Talbott verdict is the first confidence vote of 12 people in the genetic genealogy's ability to not just name a drop of blood or skin cells raised from a fingerprint a swab soaked with sperm, but to help prosecutors prove that the person behind that name also committed the crime of which she is accused. This result could have a positive impact on other cases pending in the courts of other states, even if it was only to strengthen public opinion.
But more importantly, Talbott's panting image when the jury reads his verdict tells law enforcement agencies across the country that genetic genealogy is a good thing, that it's not enough to generate clues and make arrests. And that has huge implications for both future of the fight against crime and genetic privacy.
"We did not know if you would have any skeptical evidence that the police came up with this medium, or if it would think that it's a problematic investigative tool," said Andrea Roth, director of the Center for Law. and Technology of UC Berkeley. "The essential, this tells us that we did not know yesterday, is that you can convince the jury to convict someone to find a suspect through genetic genealogy."
Roth and other legal experts have raised concerns that this new phenomenon of police searches through non-criminal databases violates the principles of informed consent and threatens the constitutional protections of citizens against warrantless searches. DNA is not like a social security number. This is an inherited substance, a code that you share (to varying degrees) with all your biological parents. So, when people agree to let the forces of order access fragments of their genome, they get them too. Even if you never do a DNA test yourself.
Estimate of researchers It will only be a few years before every white man in America can be identified this way. And unlike the types of DNA technologies used for genealogy sensitive health information.
These confidentiality issues, in particular, did not arise during the Talbott trial. His lawyers sometimes denigrated the DNA proof, blaming the state of vision in genetic tunnel once they got their tip. "They are not trying to find the killer, but rather to find the source of this DNA.They assume that it must be the same person," said defense lawyer Rachel Forde during her closing plea on Tuesday. . "If DNA alone, even if this DNA is not associated with the murder itself, is enough to condemn someone for murder nowadays, we have to be careful." But the legality of how detectives traced Talbott to this DNA in the first place has never been questioned Even before the start of the trial, both parties reached an agreement to deal with the genealogy process genetic as a tipand do not dwell on it.
Based on this information, the investigators monitored Talbott, collecting a long-sought "Person A" who had remained on Van Cuylenborg's clothes and body. A stamp taken from his cheek after his arrest also matched the sample of the crime scene. Prosecutors said that a palm print had been taken in Talbott's left hand to match a print of the van's back door that was being driven by the Canadian couple at the time of their disappearance.
Talbott 's case being settled, specialists and privacy advocates are turning to other cases that more directly challenge the constitutionality of the use of the technique by the forces of law enforcement. order. In Virginia, for example, a 37-year-old man is accused of raping a woman under the threat of a gun in 2016. The same company that worked on the Snohomish County case, Parabon Nanolabs, identified Jesse Bjerke as the alleged rapist through parents found in GEDmatch. Bjerke's lawyers seek to make this DNA evidence inadmissible.
Others do not wait for the courts to decide, but instead appeal to legislators to impose limits on how genetic genealogy can be used. These could include the limitation of the technique to violent crimes, as did the states of California for a controversial DNA match called family research. Currently there is no laws or regulations It governs how police services can use these non-criminal DNA databases, not reporting requirements that could illustrate both the success rate of the method and its extent.
These and other questions about the ability of the police to turn American citizens into genetic informants will need answers at some point. But at least for the moment, at least for the families of two children who had met one day 31 years ago and never came home, the only question that matters to them has finally been solved.
. (tagsToTranslate) DNA (t) Crime (t) ancestry (t) privacy (t) genetic</pre></pre>
It is thus that Yang began his 10 years of diversion in the world of ruminant biology. I've traveled to California to take wood tissue samples to study how these complex structures of bone, living cells and nerve endings can reach more than 50 centimeters in a season. Finally, he and his colleagues tracked down some genes responsible for this remarkable feat of regeneration. But it was a difficult and lengthy job; at the time, none had ever been sequenced on the deer genome. An international team of workers had just decoded the first bovine genomeChinese scientists have discovered the DNA of goats and sheep. In the days of still expensive sequencing, more exotic ruminants were not a top priority.
But this week, the multi-hat mammals are finally paying their dues. Thursday, a consortium of scientists led by China reported their efforts to map the genomes of 44 ruminant species, from Serengeti gazelles and buffaloes to the tiny vampiric muntjacs inhabiting the Asian jungle, to the thick fur reindeer that roam the snowy plains of the Arctic. The 44 (and some others) can be viewed and downloaded. right here, if this interests you. Along with two other papers which appear in the last issue of Scienceit represents the first results of the ruminant genome project, a data set of more than 40 trillion base pairs illustrating China's growing role as a world leader in genomics research.
The major scientific breakthrough benefits both evolutionary biologists seeking to better understand how ruminants have successfully colonized six continents with extremely different environments and breeders who wish to introduce such adaptive benefits in domesticated herds. The genetic resource may also prove useful for biomedical researchers like Yang, providing clues that may one day help humans heal faster, to keep cancerand even live healthier in space.
"The significance will be huge," said Yang, who was not involved in the RGP, but reviewed one of the group 's papers and wrote an accompanying text. article in perspective. "It is not only about solving the unresolved problem of how these species have evolved and integrating them into a family tree, but it also generates significant potential for future impact. Remember that a large number of existing genes in cows and goats as well as deer and sheep also exist in humans. "
While Yang is trying to understand why people develop osteoporosis, other researchers will likely be interested in the fact that such rapid growth does not occur. flee to become malignant tumors. Ruminants are about five times less likely to get cancer than other mammals, according to records kept by Philadelphia and San Diego zoos. This has led the RGP researchers to hypothesize that whatever genetic adaptations developed by ruminants to control their regeneration of their antlers, this also provides: a protective effect against the development of cancer.
By combining DNA sequence data with gene expression profiles of deer, goats and sheep, the consortium scientists identified a handful of genes that work together to keep these species free from cancer, even when they develop pounds of new tissue each year. It will still work to understand exactly how they work. However, a version of a tumor suppressor gene in deer is already promising enough that five of the scientists who identified it have already applied for a Chinese patent for its use as a cancer treatment.
Among these scientists are Wen Wang, a geneticist at Northwestern Polytechnical University in Xi'an, China. Wang was one of the pioneers of the first efforts to sequence goats and sheep ten years ago, when I approached BGI-Shenzhen, the largest sequencing facility in the world, on the assembly in consortium to fight against the ruminants. At the time, resources and technology limited them to finishing species important for agriculture. But Wang always hoped to grow.
By the end of 2015, he finally had the opportunity, when the NPU granted him funds to launch the project and a supercomputer to help him in the intense process of assembling trillions of genetic code strings. . I partnered with one of the world's leading ruminant experts, Rasmus Heller from the University of Copenhagen, and in early 2016 they were operational. Wang recruited former doctoral students who could have contributed to the genomes of the goat and ewe and who now operated their own laboratories. In the end, more than 20 institutions, mainly located in China, contributed to the project.
One of the biggest challenges was to get enough genetic material from all the species that they wanted to include in the study. Heller's relations in Denmark enabled the group to access a vast collection of tissues, including dozens of wild cattle, but some of them proved to be impossible to extract enough from. DNA for the sequence. They have therefore joined a more global sequencing effort called the Earth BioGenome Project to obtain additional species. For others, they sent researchers to reindeer farms in Mongolia, asked zoos to collect skin samples of rare striped antelope and asked for conservation grounds to get hold of them. small pieces of a critically endangered gazelle. They have not listed the species they have listed – muskox and a small semi-aquatic antelope called lechwe are too difficult. But, says Heller, the data set is already in high demand, which has helped launch new projects in the field of ecology and population conservation. "I hope this will trigger a golden age in genomics research on these species."
For some species, such as the polar reindeerthese sparks have already begun to fly. In one of the Science Published documents today, Heller and Wang and their colleagues have revealed how to cope with such low light levels for large parts of the year. In addition to developing supercharged genes metabolizing vitamin D to help them capture more calcium, they have also acquired many unique mutations the genes that control their circadian clocks. Learn more about these adaptations could help scientists better understand and possibly deal with seasonal affective disorder, or even design drugs to help astronauts in Mars adjust their circadian rhythms to a longer night.
Harris Lewin is an evolutionary geneticist from the University of California at Davis, who coordinates the Earth BioGenome Project, which aims to collect sequences of all living organisms from the pale blue dot. Part of the work of this US-based project is to integrate dozens of smaller, more focused sequencing efforts around the world. The trend is to see that the bulk of the money and leadership on these sequencing projects (not to mention the discoveries that they generate) are now coming from China and Europe. "All the others are saving on these efforts to produce high quality footage and we are starting to fall behind," said Lewin. "The ruminant genome project is a very good example of the Chinese, who have always been good people and are now taking the lead."
(tagsToTranslate) genetics (t) agriculture (t) cancer (t) circadian rhythm</pre></pre>
She knew it because at the time, Moore was working as a genealogical genealogy researcher on the PBS program, Find your rootsand had a counseling company helping adoptees find their biological parents. To facilitate her research, she regularly connected to GEDmatch, a public database where amateurs download the results of consumer genetic testing companies as 23andMe and ancestry find parents sharing DNA and reverse engineer their family trees. She had learned that another genealogist on the site, Barbara Rae-VenterMoore was downloading files that seemed out of place, and Moore suspected that they came from family members, but from crime scenes. But she had never imagined that any of them belonged to the man considered to be one of the most notorious serial killers of the history of the United States. -United. "It was going to be huge," she recalls telling people that day.
But even Moore could have just predicted how huge it would become. The year that has passed since the arrest of Joseph James DeAngelo, the alleged killer of the state, the genealogy of investigation has become the most powerful new tool in the fight against criminality. since the DNA itself. Until now, this technique has been used to identify suspects in over 50 other cases. Its vast potential to break tens of thousands more has given birth to a lucrative new forensic science business, the creation of police units dedicated to the construction of family trees, and the first marketing campaign of home DNA kits get people to send their spit to solve the crimes.
Practice too raises serious confidentiality issues with respect to confidentiality. Namely, only one user can unconsciously throw a web of legal suspicion hundreds of family members who did not consent to a search by the police, but have not even passed a DNA test. Today, there are no laws or policies governing how and when cops can use genealogical genealogy. Prosecutors will have to defend the constitutionality of the technique when the first cases are tried this summer; Meanwhile, law enforcement agencies are increasingly consulting consumer DNA databases to find leads, with only the terms and conditions of these websites to control them.
For companies that have benefited from this boom, however, the news has been good so far. "This is the most exciting thing that has taken place in forensic science for a long time," said Andrew Singer, director of marketing and sales for Bode Technology, the largest forensic DNA testing company. from the country. In February, Bode launched a genealogical genealogy company to compete with Parabon NanoLabs, the first private laboratory to embark on the game of genetic genealogy.
Before the Golden State Killer case, Parabon, Virginia, was known for his work. reconstruct facial sketches from the DNA of the crime scene. But in the weeks that followed, the relatively small forensic firm took on importance by hiring Moore and becoming the reference entrepreneur of the industry for the forensics of the family tree. Publicly, the company was involved in 49 identifications – 47 suspects and two does. But Moore says the real number is higher.
Her team of four genealogists have worked on 80 other files, that is, she spent up to 15 hours (and billed $ 3,500) per case on tree construction and settlement. a list of names for the investigative body. 80 others are waiting for a genealogist to make a first assessment, to see if the number of matches in GEDmatch is sufficient to deserve more work, or a police service that must sign to move to the next phase. Moore says that of the 49 positive team IDs, in one case, the name of the person with whom they were invented had already appeared in a police file.
Bode has not yet publicly revealed his own positive identifications and Singer declined to specify how many cases the company's contract genealogy team is currently working on. But he says that there is a lot of demand. Singer spoke to WIRED Tuesday in Phoenix, Arizona, where Bode is hosting its annual DNA technology conference for prosecutors and public crime lab officials. Over the past 18 years, attendance has never exceeded 275 people. This year, 400 people showed up. Most of the participants even arrived a day earlier than expected to attend a two-hour workshop on genetic genealogy. "Everyone is extremely excited about this, but we're only at the beginning," Singer said.
Lori Napolitano, chief of forensic services of the Florida Law Enforcement Department, was one of the speakers at the workshop on Tuesday. A few years ago, she founded the biological family of her biological father. She even attended a few Moore seminars. After the Golden State Killer case, she convinced her superiors to let her own genetic genealogy unit support investigations conducted by more than 300 Florida law enforcement agencies. When it was created in September, the Napolitano team became the first internal state-level genealogy unit in the country (the FBI has its own unit, trained by Barbara Rae-Venter).
In January buzzfeed revealed In addition to GEDmatch, the FBI searched the extensive genealogical database of Family Tree DNA, one of the leading private genetic testing companies. Shortly after, Genealogical Tree changed its terms of service explicitly authorize any law enforcement agency or private laboratory to represent them, to send a crime scene sample or to upload a DNA file to the database, provided that it conforms to the criteria of the company criteria. There were some initial reactions, but a Family Tree spokesperson said that only 1% of her two million clients had decided to withdraw from family reunification services that would make their profiles available to the FBI, Local order and private laboratories like Bode. . Family Tree says that the chips used by Parabon to generate a genetic profile are largely incompatible with its platform, although the two companies are currently discussing ways to solve the problem. For the moment, Parabon's research capability is limited to GEDmatch.
While Napolitano's four-person team in Florida is still working with Parabon to produce DNA profiles from old crime scene samples and upload them to GEDmatch, being able to create a large portion of their own tree building means that the state can save thousands of dollars in private laboratory contracts. fees per case. "It really brings us hope," says Ryan Backmann, founder of Cold Case Project, in Jacksonville, Florida, a non-profit victim advocacy organization. This also makes Florida an example of how other public bodies could expand their own use of the technique. "When your state lab invests in this technology, it shows that you believe that it is there for the long term and that it will solve a lot of cases."
Backmann launched the Cold Case project in 2015, while he was struggling with the case of his own father, who was icing (Cliff Backmann was killed in the back and killed during a robbery in 2009). Since then, as a result of requests for public documents and requests from families of victims, he has assembled a clearinghouse for more than 10,000 unresolved murders nationwide. Although the FBI keeps figures on unresolved murders – 250,000 of them in the United States since 1980, according to the Project of responsibility for murder-Before the Cold Case project, there was no searchable database containing the names of victims and investigative agencies. Backmann has created one to make it easier for people with tips to make themselves known.
The year following the opening of the Golden State Killer case, he made dozens of appeals to the police on behalf of family members who wanted to know if their case could be accepted as an approach to genetic genealogy. Sometimes he learns that these cases do not have any DNA evidence or that there is not enough material left to generate a genetic profile. Sometimes I discover that DNA is there, but there is not enough money in the budget agency to try it. That is why Backmann has recently started meeting potential benefactors and has launched a fund to raise funds to help law enforcement agencies investigate these cases. He added that they had not raised enough funds to advertise with agencies. Even if they could oppose nonprofit prices of Parabon or Bode, any donation not exceeding six digits "would simply disappear in a weekend," says Backmann, given the amount of l & # 39; interests. . "We feel like we are at the forefront of this wave, but for most of us, we just wait for it to be really available to the masses." , and not just as a niche. "
Before reaching the masses, legislators such as Charles Sydnor III are trying to ensure that the public has a frank discussion about what it means for the government to access consumer genetic databases filled with millions of US citizens. law-abiding. In January I introduced a bill Maryland House delegates that would have been the first law in the country to prohibit the police the use of genealogical genealogy, saying it was similar to a "genetic monitoring". But the law enforcement agencies voted against the bill (like Parabon Steven Armentrout) and he died in committee a few weeks later.
Sydnor is now planning a special interim hearing for this fall to educate his colleagues on the subject of the genetic genealogy of investigation, before trying again at the next session. As headlines multiply with new cold crates each week, I said that some of his colleagues had told him, "Charles, the genie is out of the bottle, what do you really think you can do about it? ? " Maryland has long defended the right to privacy of genetic data. In 2008, it became the only state to ban old practice of "family research""This implies that the police search the genetic records of criminals and people found guilty in trying to identify suspects through their close genetic relatives." I just wanted families of genealogy enthusiasts to benefit from same protections as families of convicted criminals. "We have had a policy for over ten years that says we should not do this," says Sydnor. "I want to catch the bad guys as much as everyone else, but there are all kinds of unintended consequences that we do not stop thinking. "
Other states are pushing their own legislation in different directions. In February, a legislator from Arizona a mandatory DNA database for the citizens of that state who could have been interrogated by the forces of the order who were investigating the crimes. Meanwhile, lawmakers in Massachusetts are drafting a bill that would dedicate genealogical genealogy for investigation as a legal practice in that state. The co-sponsors of the bill are reported working with the family of a young woman who was abducted and killed 19 years ago and whose murderer is still at large, but they could not be contacted to answer specific questions about the law Project. In addition to a total ban, some legal experts have recommended limit the practice in another way-Only violent crimes, or only after all other options have been exhausted, in the same way that California regulates family research. Some genetic counselors have advocated banning the police from using genetic profiles to search for medical information or disclose sensitive family secrets. Others said they wanted to make compassion for the mothers identified by genealogical genealogy. in case of abandoned baby.
Moore monitors all these developments. But she says she does not intend to stop using the genealogical genealogy to solve crimes unless the law requires it. His most worrying problem as the field warms up is the lack of standards. "There is no doctorate in genetic genealogy," says Moore, who, like all pioneers in the field, is a self-taught. "There is no diploma, no certification, or even certification body that can say who is qualified to handle these cases." Ms. Moore stated that she had recently approached the topic, the Certification Board of Genealogists, about to develop a separate title for the use of genealogical genealogy. for criminal investigations. But until now, the discussions have resulted in nothing.
"It's a problem because getting caught because of your job is a big issue," Moore said. While genealogical genealogists only provide leads to law enforcement agencies – they are responsible for selecting the suspect with measures to maintain order and confirmatory tests of the law. DNA – Moore begins to feel the weight of his contributions. And she begins to think about how she can use her skills not only to help good people get behind bars, but also to incarcerate them wrongly.
Two weeks ago, she met the Innocence Project on how to exploit how post-conviction lawyers could obtain court orders so that the DNA of the crime scene sent to Parabon is transformed into uploaded files in GEDmatch. "The process would be the same, but the goal would be very different," she says. "This has not happened yet, but I think it has a lot of potential to reverse genetic genealogy as a tool for clarifying the innocent." It's an intriguing idea. But at least for the moment, there is a lot more money to be made – and a lot more political will to use it – to lock people up.
It was with the memory of the families that he could not help to keep in mind that Peranteau joined a small group of scientists who were trying to change the situation. field of gene editing to the uterus. This edition in humans is still far from being realized, but a series of recent advances in mouse studies highlights its potential benefits compared to other methods of research. 39, use of Crispr cut off diseases. Parents facing a in utero diagnoses often face only two options: terminate the pregnancy or prepare to take care of a child that may require several invasive surgeries during their lifetime just to survive. Prenatal gene editing may offer a third potential path. "What we see as the future is a minimally invasive way of treating these abnormalities for their genetic origin," Peranteau said.
To prove this vision, Peranteau and colleagues at the University of Pennsylvania injected Crisp-encoded virus-coding components into the placenta of pregnant mice whose unborn babies had a mutation that caused lung disease. deadly. When the fetuses breathed in the amniotic fluid, they also inhaled the Crispr bit, which set to work to modify the DNA within their rapidly dividing alveolar progenitor cells. These cells give rise to many types of cells that line the lungs, including the secretion of a sticky substance that prevents the lungs from collapsing each time you breathe. Mutations in the proteins that make up this secretion are a major source of congenital respiratory disorders. All mice carrying the mutation died a few hours after birth. About a quarter of those published with Crispr survived. The results were published in today's issue of Translational medicine science.
This is the second proof of concept of the group of scientists of the past year. In October, they published an article describing a slightly different procedure for editing mutations leading to a lethal metabolic disorder. By transition to a single base In prenatal mouse liver cells, the Peranteau team was able to save almost all the raccoons. Other recent successes include the mice to be born cured of a blood disorder called beta-thalassemia following a prenatal injection of Crispr, performed last year by a team of Yale and Carnegie Mellon.
Although the field is still in its infancy, its pioneers believe that many problems Crispr-based therapies have to face to reach like enough good cellsand evade the human immune system – can be solved by treating patients while they are still in the womb.
"If you're trying to change cells in an adult organ, they're not proliferating, so you have to reach a lot to make an impact," says Edward Morrisey, a cardiologist at the University of Pennsylvania, co-author of the latest study. The fetuses, on the other hand, continue to develop, which means that their cells divide rapidly to develop into new tissues. The sooner you can edit, the more these genetic changes will multiply and spread in developing organs. Morrisey's mice may have been born with genetic editing only in about 20% of their lung cells, but 13 weeks later the correction was extended to the entire lung surface . "They have actually passed unedited cells because these cells are very sick," Morissey said.
For lung diseases in particular, this represents a considerable advantage. As soon as a baby leaves the watery world of the uterus, his lung cells begin to secrete a mucus barrier mixed with a surfactant, to prevent dust, viruses or other foreign objects, including including Crispr components, to reach these tissues. A developing fetus also has a less aggressive immune system than a human being exposed to the outside world. It is therefore less likely to attack the components of Crispr, which, after all, come from the bacterial kingdom.
Now, you may think that if editing earlier is better, why not edit an embryo right after fertilization, when it is only one cell or two years old? But this technique, known as germline modification (you may remember it from Chinese scandal of babies Crispr), is much more complicated ethical effort. Editing at this point would forward all changes to all cell, including those that produce sperm or eggs. In the United States, this type of montage is actually banned as a result of a congressional directive to the US Food and Drug Administration prohibiting any clinical trial involving genetically modified human embryos. (The ban, which was renewed each year, was last reaffirmed in February 2019). The other thing is that having a precise diagnosis when an embryo consists of only a few old cells can be tricky. Waiting long enough to visualize the fetus and other vital signs can provide important clues to the severity of the disease. "This puts us in this ideal place to treat an illness early, that is, as soon as it is diagnosed," said Peranteau.
But there are still security issues to solve. On the one hand, editing in utero involves two patients, not one. In the process of healing a child, this technique would potentially expose people to good healththe mother-A treatment that does not provide any potential benefit and only involves potential risks, including dangerous immune reactions. And because the update takes place in its reproductive system, some components of Crisp can make their way into the fallopian tubes and into its ovaries, potentially altering other unfertilized eggs. Much more scientific research will be needed to better assess these risks. To give you an idea of how long it may take, consider in utero gene therapy –an older approach this involves replacing a defective gene with a functional gene using a virus – first proposed in the mid-1990s following a series of positive proof-of-concept studies in mice. Today, only one single clinical trial is in progress
"This is not a panacea for curing all existing genetic diseases," said Peranteau. But I think that a Crispr approach will be able to piggyback on the work of the field of gene therapy and could offer a new way forward for at least some of their patients. "In the future, not tomorrow or the next day, in years, I think that publishing in utero would give hope to families who today do not have one."