Genetic engineers at the lab used the new tool to generate a catalog of 71 million possible missense variants, classifying 89% as either benign or pathogenic
Genetic engineers continue to use artificial intelligence (AI) and deep learning to develop research tools that have implications for clinical laboratories. The latest development involves Google’s DeepMind artificial intelligence lab which has created an AI tool that, they say, can predict whether a single-letter substitution in DNA—known as a missense variant (aka, missense mutation)—is likely to cause disease.
The Google engineers used their new model—dubbed AlphaMissense—to generate a catalog of 71 million possible missense variants. They were able to classify 89% as likely to be either benign or pathogenic mutations. That compares with just 0.1% that have been classified using conventional methods, according to the DeepMind engineers.
This is yet another example of how Google is investing to develop solutions for healthcare and medical care. In this case, DeepMind might find genetic sequences that are associated with disease or health conditions. In turn, these genetic sequences could eventually become biomarkers that clinical laboratories could use to help physicians make earlier, more accurate diagnoses and allow faster interventions that improve patient care.
“AI tools that can accurately predict the effect of variants have the power to accelerate research across fields from molecular biology to clinical and statistical genetics,” wrote Google DeepMind engineers Jun Cheng, PhD (left), and Žiga Avsec, PhD (right), in a blog post describing the new tool. Clinical laboratories benefit from the diagnostic biomarkers generated by this type of research. (Photo copyrights: LinkedIn.)
AI’s Effect on Genetic Research
Genetic experiments to identify which mutations cause disease are both costly and time-consuming, Google DeepMind engineers Jun Cheng, PhD, and Žiga Avsec, PhD, wrote in a blog post. However, artificial intelligence sped up that process considerably.
“By using AI predictions, researchers can get a preview of results for thousands of proteins at a time, which can help to prioritize resources and accelerate more complex studies,” they noted.
Of all possible 71 million variants, approximately 6%, or four million, have already been seen in humans, they wrote, noting that the average person carries more than 9,000. Most are benign, “but others are pathogenic and can severely disrupt protein function,” causing diseases such as cystic fibrosis, sickle-cell anemia, and cancer.
“A missense variant is a single letter substitution in DNA that results in a different amino acid within a protein,” Cheng and Avsec wrote in the blog post. “If you think of DNA as a language, switching one letter can change a word and alter the meaning of a sentence altogether. In this case, a substitution changes which amino acid is translated, which can affect the function of a protein.”
In the Google DeepMind study, AlphaMissense predicted that 57% of the 71 million variants are “likely benign,” 32% are “likely pathogenic,” and 11% are “uncertain.”
The AlphaMissense model is adapted from an earlier model called AlphaFold which uses amino acid genetic sequences to predict the structure of proteins.
“AlphaMissense was fed data on DNA from humans and closely related primates to learn which missense mutations are common, and therefore probably benign, and which are rare and potentially harmful,” The Guardian reported. “At the same time, the program familiarized itself with the ‘language’ of proteins by studying millions of protein sequences and learning what a ‘healthy’ protein looks like.”
The model assigned each variant a score between 0 and 1 to rate the likelihood of pathogenicity [the potential for a pathogen to cause disease]. “The continuous score allows users to choose a threshold for classifying variants as pathogenic or benign that matches their accuracy requirements,” Avsec and Cheng wrote in their blog post.
However, they also acknowledged that it doesn’t indicate exactly how the variation causes disease.
The engineers cautioned that the predictions in the catalog are not intended for clinical use. Instead, they “should be interpreted with other sources of evidence.” However, “this work has the potential to improve the diagnosis of rare genetic disorders, and help discover new disease-causing genes,” they noted.
Genomics England Sees a Helpful Tool
BBC noted that AlphaMissense has been tested by Genomics England, which works with the UK’s National Health Service. “The new tool is really bringing a new perspective to the data,” Ellen Thomas, PhD, Genomics England’s Deputy Chief Medical Officer, told the BBC. “It will help clinical scientists make sense of genetic data so that it is useful for patients and for their clinical teams.”
AlphaMissense is “a big step forward,” Ewan Birney, PhD, Deputy Director General of the European Molecular Biology Laboratory (EMBL) told the BBC. “It will help clinical researchers prioritize where to look to find areas that could cause disease.”
Other experts, however, who spoke with MIT Technology Review were less enthusiastic.
Heidi Rehm, PhD, co-director of the Program in Medical and Population Genetics at the Broad Institute, suggested that the DeepMind engineers overstated the certainty of the model’s predictions. She told the publication that she was “disappointed” that they labeled the variants as benign or pathogenic.
“The models are improving, but none are perfect, and they still don’t get you to pathogenic or not,” she said.
“Typically, experts don’t declare a mutation pathogenic until they have real-world data from patients, evidence of inheritance patterns in families, and lab tests—information that’s shared through public websites of variants such as ClinVar,” the MIT article noted.
Is AlphaMissense a Biosecurity Risk?
Although DeepMind has released its catalog of variations, MIT Technology Review notes that the lab isn’t releasing the entire AI model due to what it describes as a “biosecurity risk.”
The concern is that “bad actors” could try using it on non-human species, DeepMind said. But one anonymous expert described the restrictions “as a transparent effort to stop others from quickly deploying the model for their own uses,” the MIT article noted.
And so, genetics research takes a huge step forward thanks to Google DeepMind, artificial intelligence, and deep learning. Clinical laboratories and pathologists may soon have useful new tools that help healthcare provider diagnose diseases. Time will tell. But the developments are certain worth watching.
Millions of cancelled healthcare appointments and lengthy waits for care abound in UK, New Zealand, and in the US
Strikes continue on multiple continents as thousands of healthcare workers walk off the job. Doctors, medical laboratory scientists, nurses, phlebotomists and others around the world have taken to the picket lines complaining about low wages, inadequate staffing, and dangerous working conditions.
In England, junior doctors (the general equivalent of medical interns in the US) continue their uphill battle to have their complaints heard by the UK government. As a result, at hospitals and clinics throughout the United Kingdom, more than one million appointments have been cancelled due to strikes, according to the BBC.
“The true scale of the disruption is likely to be higher—many hospitals reduce bookings on strike days to minimize last-minute cancellations,” the BBC reported. “A total of one million hospital appointments have had to be rescheduled along with more than 60,000 community and mental health appointments since December [2022], when industrial action started in the National Health Service (NHS).”
According to The Standard, “Consultants in England are to be re-balloted over the prospect of further strike action as doctors and the government remain in talks with a view to end the dispute. The British Medical Association (BMA) said that specialist, associate specialist, and specialty (SAS) doctors will also be balloted over potential strike action.”
“We must be prepared to take the next step and ballot for industrial action if we absolutely have to—and we will do this … if upcoming negotiations fail to achieve anything for our profession,” Ujjwala Anand Mohite, DRCPath, FEBPath (above), a histopathologist at the NHS, Dudley Group of Hospitals, and the first female Chair of the SAS committee UK, told The Guardian.
New Zealand Doctors, Clinical Laboratory Workers Strike
In September, the first-ever nationwide senior doctor strike occurred in New Zealand and was then followed by another strike of about 5,000 doctors and 100 dentists from New Zealand’s public hospitals, the World Socialist Web Site reported.
Similar to the UK, the strikes reflect mounting frustration over pay not keeping up with inflation and “decades of deteriorating conditions in the public health system,” the WSWS noted.
This follows months of strikes by the island nation’s medical laboratory workers, which are ongoing.
“Our pay scales, if you compare them internationally, are not competitive. About half of our specialists come from abroad, so it’s quite important for the country’s health system to be able to attract and keep people,” Andy Davies, a lung specialist who joined the picket outside 484-bed Wellington Hospital, told the WSWS.
“We’re not asking for the world, we’re asking for an inflationary pay rise, and we haven’t had an inflationary pay rise year-on-year, and it’s beginning to show,” he added.
“What type of health system do they want?” he continued. “Do we want one that treats all people and manages what they need, or do we want a hacked down system that does less?”
The conflicts over pay and working conditions have caused many healthcare workers in New Zealand to leave the field entirely. This has led to severe shortages of qualified workers.
“Patient waiting times—for cancer, hip replacements, cardiac problems, and many other conditions—have exploded due to understaffed and overwhelmed hospitals,” the WSWS reported.
US Healthcare Workers also Striking
The US has its share of striking healthcare workers as well. Healthcare Dive tracked 23 ongoing or anticipated strikes throughout the nation’s healthcare industry since January 1, 2023. In 2022, there were 15 strikes of healthcare workers at the nation’s hospitals and health systems.
These walkouts include doctors, nurses, pharmacy workers, imaging specialists, and thousands of frontline healthcare workers striking over dangerously low staffing levels, unsafe working conditions, and low pay.
In October, 75,000 nurses, support staff, and medical technicians from Kaiser Permanente participated in a 72-hour strike comprised of hundreds of hospitals and clinics throughout California, Washington state, Oregon, Virginia, and the District of Columbia, Reuters reported.
The three-day strike, “Marked the largest work stoppage to date in the healthcare sector,” Reuters noted. Doctors, managers, and contingency workers were employed to keep hospitals and emergency departments functioning.
“The dispute is focused on workers’ demands for better pay and measures to ease chronic staff shortages and high turnover that union officials say has undermined patient care at Kaiser,” Reuters stated.
Staffing shortages following the COVID-19 pandemic are partly to blame for current struggles, but contract staffing to fill critical positions has exacerbated the problem.
“Kaiser’s outsourcing of healthcare duties to third-party vendors and subcontractors has also emerged as a major sticking point in talks that have dragged on for six months. … The clash has put Kaiser Permanente at the forefront of growing labor unrest in the healthcare industry—and across the US economy—driven by the erosion of workers’ earning power from inflation and pandemic-related disruptions in the workforce,” Reuters noted.
Across the globe, many healthcare workers—including clinical laboratory scientists in countries like New Zealand—are feeling burnt out from working in understaffed departments for inadequate pay. Hopefully, in response to these strikes, governments and healthcare leaders can come to resolutions that bring critical medical specialists back to work.
More than 10,000 doctors walked out for the second time in two months, further burdening an already overwhelmed NHS
On April 11, tens of thousands of junior doctors (similar to medical residents in the US) left their posts in British hospitals commencing a four-day walkout. The strike resulted in the cancellation of thousands of operations and appointments, as well as cancelling or delaying thousands of clinical laboratory tests and anatomic pathology readings associated with those healthcare visits and surgical procedures.
The walkout was spurred by pay concerns and working conditions and comes on the heels of a three-day strike last month. That strike had already weakened the UK’s frail National Health System (NHS), which has become inundated with appointment backlogs that predate the COVID-19 pandemic, and which has led to longer wait times to see a doctor, ABC News reported.
This latest strike was more perilous since the senior doctors who covered for their juniors during last month’s strike were previously on leave for a holiday weekend, United Press International (UPI) reported.
“These strikes are going to have a catastrophic impact on the capacity of the NHS to recover,” Matthew Taylor (above), Chief Executive of the NHS Confederation, told Sky News. “The health service has to meet high levels of demand at the same time as making inroads into that huge backlog … That’s a tough thing to do at the best of times—it’s impossible to do when strikes are continuing.” (Photo copyright: Wikimedia Commons.)
Junior Docs Cite Injustice
Junior doctors who walked out are calling for a 35% pay raise to right the wrongs of 15 years of below-inflation raises, but the government continues to argue it cannot afford to increase pay, UPI noted.
“There is nothing ‘junior’ about the work I have done as a doctor. For an hour of work that I might save a life, I can be paid 19£ [$23.65],” said Jennifer Barclay, MD, a surgical junior doctor in the UK’s North West electoral zone, in a British Medical Association (BMA) press release.
“My dad, an electrician, tells me to quit and retrain in his footsteps. I’d be earning more, have less stress, less responsibility, better hours, and a better work-life balance after three years,” she added. “Surely, this life, this training, responsibility, debt, and crushing workload is worth more than 19£ per hour? I’ll be on the picket line this week because doctors believe that it is.”
According to the BMA, newly qualified junior doctors earn just over 14£ ($17.43) per hour, ABC News reported, which added, “The doctors’ union has asked for a 35% pay rise to bring junior doctor pay back to 2008 levels.”
However, their pay demands come in the midst of a cost-of-living crisis in the UK. Inflation has risen above 10%. Paired with increases in heating costs and food prices mean that decreased wages leave many struggling to pay bills, ABC news reports.
A hard-hitting BMA advertising campaign designed to shine light on these disparities depicts three junior doctors (with one-, seven-, and 10-years’ experience) removing an appendix. The video shows that the total the three would be paid for the hour-long operation would be 66.55£ ($82.84):
Doctor with one year experience: 14.09£ ($17.54).
Doctor with two years’ experience: 24.46£ ($30.45).
Doctor with three years’ experience: 28£ ($34.85).
And this for performing a potentially life-saving procedure, the BMA stated.
In the press release, BMA Junior Doctors Committee co-chairs Robert Laurenson and Vivek Trivedi said, “It is appalling that this government feels that paying three junior doctors as little as 66.55£ between them for work of this value is justified. This is highly skilled work requiring years of study and intensive training in a high-pressure environment where the job can be a matter of life or death.”
Patient Care is Affected
Lower salaries also affect patient care levels and have led to recruitment issues, with many doctors leaving the profession, the BBC reported. “This is not a situation where we are fixed in our position. We’re looking for negotiations and Steve Barclay (UK’s Secretary of State for Health and Social Care) isn’t even willing to talk to us. He hasn’t put any offer at all on the table … there has to be two sides in the discussion,” Emma Runswick, MD, a junior doctor and deputy chairwoman of the BMA, told the BBC.
But while the junior doctors battle for wages, the government’s initial focus has been on patient wellbeing. “There will be risks to patient safety, risks to patient dignity, as we are not able to provide the kind of care we want to,” NHS Confederation Chief Executive Matthew Taylor told UPI prior to the walkout.
The timing of the walkout also caused consternation with the NHS. “Not only will walkouts risk patient safety, but they have been timed to maximize disruption after the Easter break,” Health Secretary Barclay told UPI as the walkout was announced.
Barclay also claimed the amount sought by doctors was “unreasonable” and would cause raises above $25,000 per year, UPI reported. “If the BMA is willing to move significantly from this position and cancel strikes, we can resume confidential talks and find a way forward as we have done with other unions,” he stated.
It is important to note that doctors would be pulled from picket lines if immediate danger were present due to trade union laws that say life-and-limb coverage must be provided, the BMA told the BBC.
Officials also worry about diminishing smallpox vaccinations, which offered people protection against the infectious disease
Monkeypox challenges from the current outbreak have dogged public health agencies even though the disease was first identified more than 50 years ago. That is because the virus has found new avenues of infection. These developments will be relevant for the nation’s clinical laboratories, which are often the first healthcare providers to confirm a suspected case is positive for monkeypox and notify a public health laboratory about the positive test result.
The latest monkeypox numbers from the federal Centers for Disease Control and Prevention (CDC) indicate that, as of September 6, the US has identified 19,962 cases in the 2022 outbreak, while worldwide the case number is 52,037.
In “When It Comes to Monkeypox Testing, Clinical Laboratories Should Be Aware of Five Significant Developments,” Dark Daily wrote about steps being taken to identify and control infections in America as well as trends in medical laboratory testing for monkeypox. This included reports of phlebotomists refusing to draw monkeypox blood samples and how social stigma surrounding the disease can affect who gets a medical laboratory test.
Workers at clinical laboratories and anatomic pathology groups will gain from understanding why monkeypox has spread beyond its traditional geography.
“Monkeypox symptoms include swollen lymph nodes, fever, and body aches that result in red bumps on hands, feet, mouth, and genitals,” Bodhraj Acharya, PhD (above), of the Laboratory Alliance of Central New York, told Dark Daily. “It spreads by close contact, respiratory droplets, lesions, and bodily fluids.” Clinical laboratories engaged in testing for monkeypox will want to stay alert to patients presenting with such symptoms. (Photo copyright: Laboratory Alliance of Central New York.)
African Public Health Officials Saw New Monkeypox Challenges Coming
Researchers and public health experts have been perplexed about how and why the latest monkeypox outbreak has occurred so aggressively beyond its origin in rural Central Africa.
“Monkeypox is caused by the pox virus, with a close resemblance to smallpox,” said Bodhraj Acharya, PhD, Manager of Chemistry and Referral Testing at the Laboratory Alliance of Central New York, in a conversation with Dark Daily. “Unlike COVID-19, this is an old enemy which has roots in the 1970s from Congo, when the disease was erratically endemic in Africa.”
According to the World Health Organization (WHO), most monkeypox cases since 1970 have been reported from rural rainforest regions in Central and Western Africa.
Thus, a monkeypox outbreak occurring in Europe and the United States in 2022 has puzzled virologists and microbiologists because it does not follow the historical pattern of the virus’ spread. For example, the first monkeypox case in the US arrived in May from a Massachusetts patient who had traveled to Canada, a state press release noted.
Before the Nigerian outbreak, the virus rose from rural areas where hunters came in close contact with animals. The illness resulted in lesions on the face, hands, and feet, Nature wrote of Yinka-Ogunleye’s recollections.
However, after 2017, she and other epidemiologists warned peers that the virus was spreading in new ways and in urban settings. For example, infected people sometimes had genital lesions, suggesting that the virus might spread through human sexual contact.
Now, in 2022, “the world is paying the price for not having responded adequately” in 2017, Yinka-Ogunleye told Nature.
Lack of Smallpox Vaccination Increases Monkeypox Challenges
The waning effects of smallpox vaccinations, which ended in 1980 after smallpox was basically eradicated from the world, may have opened the door for monkeypox to spread earlier this year. Smallpox vaccines provided some protection against monkeypox, but by now three generations of people have not received smallpox inoculations.
“Eyebrows were raised when multiple cases of monkeypox were reported from various non-endemic countries starting in May of 2022,” Acharya said. “Due to genetic similarity, smallpox vaccination provided some cross-protection, but the termination of smallpox vaccination could have provided ground for the recent insurgence and spread of monkeypox.”
Trying to jumpstart a new monkeypox vaccination campaign on the heels of COVID-19 shots may be met with resistance from a virus-weary public. But other options at preventing the current spread of monkeypox may present challenges as well, such as trying to curtail sexual activity among affected population, the BBC reported.
“The easiest way to prevent it is to close down all highly active sexual networks for a couple of months until it goes away, but I don’t think that will ever happen. Do you?” Paul Hunter, PhD, Professor of Medicine at the University of East Anglia in Norwich, England, told the BBC.
For medical laboratory workers and others who may find themselves testing for the disease in the future, the biggest lessons from current monkeypox challenges are twofold: The virus has invaded new geography, and discontinued smallpox vaccination campaigns may have left younger people exposed to monkeypox.
Sophisticated cyberattacks have already hit hospitals and healthcare networks in Oregon, California, New York, Vermont, and other states
Attention medical laboratory managers and pathology group administrators: It’s time to ramp up your cyberdefenses. The FBI, the federal Department of Health and Human Services (HHS), and the federal Cybersecurity and Infrastructure Security Agency (CISA) issued a joint advisory (AA20-302A) warning US hospitals, clinical laboratories, and other healthcare providers to prepare for impending ransomware attacks, in which cybercriminals use malware, known as ransomware, to encrypt files on victims’ computers and demand payment to restore access.
The joint advisory, titled, “Ransomware Activity Targeting the Healthcare and Public Health Sector,” states, “CISA, FBI, and HHS have credible information of an increased and imminent cybercrime threat to US hospitals and healthcare providers.” It includes technical details about the threat—which uses a type of ransomware known as Ryuk—and suggests best practices for preventing and handling attacks.
In his KrebsOnSecurity blog post, titled, “FBI, DHS, HHS Warn of Imminent, Credible Ransomware Threat Against U.S. Hospitals,” former Washington Post reporter, Brian Krebs, wrote, “On Monday, Oct. 26, KrebsOnSecurity began following up on a tip from a reliable source that an aggressive Russian cybercriminal gang known for deploying ransomware was preparing to disrupt information technology systems at hundreds of hospitals, clinics, and medical care facilities across the United States. Today, officials from the FBI and the US Department of Homeland Security hastily assembled a conference call with healthcare industry executives warning about an ‘imminent cybercrime threat to US hospitals and healthcare providers.’”
Krebs went on to reported that the threat is linked to a notorious cybercriminal gang known as UNC1878, which planned to launch the attacks against 400 healthcare facilities.
Clinical Labs, Pathology Groups at Risk Because of the Patient Data They Keep
Hackers initially gain access to organizations’ computer systems through phishing campaigns, in which users receive emails “that contain either links to malicious websites that host the malware or attachments with the malware,” the advisory states. Krebs noted that the attacks are “often unique to each victim, including everything from the Microsoft Windows executable files that get dropped on the infected hosts to the so-called ‘command and control’ servers used to transmit data between and among compromised systems.”
Charles Carmakal, SVP and Chief Technology Officer of cybersecurity firm Mandiant told Reuters, “UNC1878 is one of the most brazen, heartless, and disruptive threat actors I’ve observed over my career,” adding, “Multiple hospitals have already been significantly impacted by Ryuk ransomware and their networks have been taken offline.”
John Riggi (above), senior cybersecurity adviser to the American Hospital Association (AHA), told the AP, “We are most concerned with ransomware attacks which have the potential to disrupt patient care operations and risk patient safety. We believe any cyberattack against any hospital or health system is a threat-to-life crime and should be responded to and pursued as such by the government.” Hospital-based medical laboratories and independent clinical laboratories that interface with hospital networks should be assess their vulnerability to cyberattacks and take appropriate steps to protect their patients’ data. (Photo copyright: American Hospital Association.)
Multiple Healthcare Provider Networks Under Attack
Hospitals in Oregon, California, and New York have already been hit by the attacks, Reuters reported. “We can still watch vitals and getting imaging done, but all results are being communicated via paper only,” a doctor at one facility told Reuters, which reported that “staff could see historic records but not update those files.”
Some of the hospitals that have reportedly experienced cyberattacks include:
In October, the Associated Press (AP) reported that a recent cyberattack disrupted computer systems at six hospitals in the University of Vermont (UVM) Health Network. The FBI would not comment on whether that attack involved ransomware, however, it forced the UVM Medical Center to shut down its computer system and reschedule elective procedures.
Threat intelligence analyst Allan Liska of US cybersecurity firm Recorded Future told Reuters, “This appears to have been a coordinated attack designed to disrupt hospitals specifically all around the country.”
He added, “While multiple ransomware attacks against healthcare providers each week have been commonplace, this is the first time we have seen six hospitals targeted in the same day by the same ransomware actor.”
An earlier ransomware attack in September targeted 250 healthcare facilities operated by Universal Health Services Inc. (UHS). A clinician at one facility reported “a high-anxiety scramble” where “medical staff could not easily see clinical laboratory results, imaging scans, medication lists, and other critical pieces of information doctors rely on to make decisions,” AP reported.
Outside of the US, a similar ransomware attack in October at a hospital in Düsseldorf, Germany, prompted a homicide investigation by German authorities after the death of a patient being transferred to another facility was linked to the attack, the BBC reported.
CISA, FBI, HHS, Advise Against Paying Ransoms
To deal with the ransomware attacks, CISA, FBI, and HHS advise against paying ransoms. “Payment does not guarantee files will be recovered,” the advisory states. “It may also embolden adversaries to target additional organizations, encourage other criminal actors to engage in the distribution of ransomware, and/or fund illicit activities.” The federal agencies advise organizations to take preventive measures and adopt plans for coping with attacks.
The advisory suggests:
Training programs for employees, including raising awareness about ransomware and phishing scams. Organizations should “ensure that employees know who to contact when they see suspicious activity or when they believe they have been a victim of a cyberattack.”
Regular backups of data and software. These should be “maintained offline or in separated networks as many ransomware variants attempt to find and delete any accessible backups.” Personnel should also test the backups.
Continuity plans in case information systems are not accessible. For example, organizations should maintain “hard copies of digital information that would be required for critical patient healthcare.”
“Without planning, provision, and implementation of continuity principles, organizations may be unable to continue operations,” the advisory states. “Evaluating continuity and capability will help identify continuity gaps. Through identifying and addressing these gaps, organizations can establish a viable continuity program that will help keep them functioning during cyberattacks or other emergencies.”
Dark Daily Publisher and Editor-in-Chief, Robert Michel, suggests that clinical laboratories and anatomic pathology groups should have their cyberdefenses assessed by security experts. “This is particularly true because the technologies and methods used by hackers change rapidly,” he said, “and if their laboratory information systems have not been assessed in the past year, then this proactive assessment could be the best insurance against an expensive ransomware attack a lab can purchase.”
