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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Clinical Lab 2.0 Advances as Project Santa Fe Foundation Secures Nonprofit Status, Prepares to Share Case Studies of Medical Laboratories Getting Paid for Adding Value

Clinical laboratory leaders interested in positioning their labs to be paid for added-value services will get knowledge, insights, and more at upcoming third annual Clinical Lab 2.0 Workshop in November

It’s a critical time for medical laboratories. Healthcare is transitioning from a fee-for-service payment system to new value-based payment models, creating disruption and instability in the clinical lab test market. In addition, payers are cutting reimbursement for many lab tests.

These are among the market factors leading some pathologists and clinical lab leaders to seek new or alternative sources of revenue to keep the lights on and the machines running in their laboratories. Some might say, it’s a dark time for the lab industry.

However, in an exclusive interview with Dark Daily, Khosrow Shotorbani, President and Executive Director of the Project Santa Fe Foundation (PSFF) and founder of the Clinical 2.0 movement, said clinical laboratories should not fear the future. 

“This is not the time to be shy or timid,” he declared. “The quantitative value of medical laboratory domain is significant and will be lost if not exploited or leveraged.”

Shotorbani has reason to be positive. In recent years the Project Santa Fe Foundation (PSFF) has emerged to advocate for, and teach, the Clinical Lab 2.0 model. Clinical Lab 2.0 is an approach which focuses on longitudinal clinical laboratory data to augment population health in new payment arrangements.

Earlier this year, PSFF filed for 501(c) status, according to a news release. It is now positioned as a nonprofit organization, guided by a board of directors whose mission is “to create a disruptive value paradigm and alternative payment model that defines placement of diagnostic services in healthcare.”

Progressing Toward Clinical Lab 2.0

At the 24th Annual Executive War College on Lab and Pathology Management held in New Orleans last May, the nation’s first ever Clinical Lab 2.0 “Shark Tank” competition was won by Aspenti Health, a full-service diagnostic laboratory specializing in toxicology screening.

“This project, as well as all of the other cases that were presented, were quite strong and all were aligned with the mission of the Clinical Lab 2.0 movement,” said Shotorbani, in a news release. “This movement transforms the analytic results from a laboratory into actionable intelligence at the patient visit in partnership with front-liners and clinicians—allowing for identification of patient risks—and arming providers with insights to guide therapeutic interventions.

“Further, it reduces the administrative burden on providers by collecting SDH [social determinants of health] predictors in advance and tying them to outcomes of interest,” he continued. “By bringing SDH predictors to the office visit, it enables providers to engage in SDH without relying on their own data collection—a current care gap in many practices. The lab becomes a catalyst helping to manage the population we serve.”

Aspenti Health’s Shark Tank entry, “Integration of the Clinical Laboratory and Social Determinants of Health in the Management of Substance Use,” focused on the social factors tied to the co-use of opioids and benzodiazepines, a combination that puts patients at higher risk of drug-related overdose or death.

The project revealed that the top-two predictors of co-use were the prescribing provider practice and the patient’s age.

“They did an interesting thing—what clinical laboratories alone cannot do—the predictive value of lab test data mapped by zip code for patients admitted in partnership with social determinants of health. This helps to create delivery models to potentially help prevent opioid overdose,” said Shotorbani, who sees economic implications for chronic conditions.

“If clinical laboratories have that ability to do that in acute conditions such as opioid overdose, what is our opportunity to use lab test data in chronic conditions, such as diabetes? The cost of healthcare is in chronic conditions, and that is where clinical lab data has an essential role—to support early detection and early prevention,” he added.

“This is often described as the transition from volume to value because this trend will fundamentally change how all clinical laboratories and anatomic pathology groups are paid,” said Khosrow Shotorbani (above), MBA, MT(ASCP), Executive Director of the Project Santa Fe Foundation (PSFF), during his presentation at the 22nd annual Executive War College in New Orleans. “This shift from volume to value also will create new winners and losers in the clinical lab industry,” he declared. “Not every lab organization will take the timely action required to introduce the value-based laboratory testing services that hospitals, physicians, and payers will need. (Photo copyright: Albuquerque Business First.)

Clinical Laboratory Data is Health Business Data

One clinical laboratory working toward that opportunity is TriCore Reference Laboratories in Albuquerque, N.M. It recently launched Diagnostic Optimization with the goal of improving the health of their communities.

“TriCore turned to this business model,” Shotorbani explained. “It is actively pursuing the strategy of intervention, prevention, and cost avoidance. TriCore is in conversation with health plans on how its lab test data and other data sets can be combined and analyzed to risk-stratify a population and to identify care gaps and assist in closing gaps.

“Further, TriCore is identifying high-risk patients early before they are admitted to hospitals and ERs—the whole notion of facilitating intervention between the healthcare provider and the potential person who may get sick,” he added. “These are no longer theoretical goals. They are realizations. Now the challenge is for Project Santa Fe to help other lab organizations develop similar value-added collaborations in their communities.”

Renee Ennis, TriCore’s Chief Financial Officer, told American Healthcare Leader, “Women go in (to an ER) for some condition, and the lab finds out they are pregnant before anyone else,” she said, adding that TriCore reaches out to insurers who can offer care coordinators for prenatal services.

“There is definitely a movement within the industry in this direction [of Clinical Lab 2.0],” she added. “But others might not be moving as quickly as we are. As a leader in this transition, I think a lot of eyes are on what we are doing and how we are doing it.”

Why Don’t More Lab Leaders Move Their Labs to Clinical Lab 2.0?

So, what holds labs back from pursing Clinical Lab 2.0? Shotorbani pointed to a couple of possibilities:

  • A lab’s traditional focus on volume while not developing partnerships (such as with pharmacy colleagues) inside the organization; and
  • Limited longitudinal data due to a provider’s sale of lab outreach services or outsourcing the lab.

“The whole notion of Clinical Lab 2.0 is basically connecting the longitudinal data—the Holy Grail of lab medicine. That is the business model. Without the longitudinal view, the ability to become a Clinical Lab 2.0 is extremely limited,” added Shotorbani.

New Clinical Lab 2.0 Workshop Focuses on Critical ‘Pillars’

Project Santa Fe Foundation will host the Third Annual Clinical Lab. 2.0 Workshop in Chicago on November 3-5. New this year are sessions aligned with Clinical Lab 2.0 “pillars” of leadership, standards, and evidence. The conference will feature panels addressing:

Click here to register online for this informative workshop, or place this URL in your browser https://dark.regfox.com/clinical-lab-20-workshop-by-project-santa-fe-foundation.

—Donna Marie Pocius

Related Information:

Project Santa Fe Foundation Files for 501( c) Status, Expands Board of Directors

Aspenti Health Wins Clinical Lab 2.0 Innovation Award Demonstrating the Clinical Laboratory as a First Responder to the Opioid Crisis

Renee Ennis Wants Lab to A Have a Seat at the Table

Aspenti Health Takes Home Grand Prize in Nation’s First Clinical Lab 2.0 Shark Tank Competition Showcasing Added Value, Clinical Success Stories

Federal Judge Blocks New HHS Rule That Would Have Required Pharmaceutical Companies to Include Pricing in Television Ads

Drug companies claim HHS rule violates their first amendment rights, but added web links to drug prices in their TV ads anyway

Will American consumers ever see the prices of their prescription drugs? That almost happened this summer, when a Trump administration healthcare transparency initiative would have required pharmaceutical companies to include prices in drug advertisements. But that requirement was halted by a federal judge one day before it was scheduled to take effect.

The measure, which passed in May, was intended to provide healthcare consumers with price transparency for some prescription medications and help lower prescription costs. However, a federal judge placed the new law on hold citing government over-reach.

This is a significant development for clinical laboratory managers, pathologists, and others watching efforts that will enable patients to see the cost of their medical care in advance of service. Also, few were surprised to learn that this court case was filed by pharmaceutical companies with the goal of preventing prescription drug prices from being disclosed in these advertisements.

HHS Tells Big Pharma to ‘Level with People’ About Drug Costs

Reducing prescription drug prices is a critical issue for healthcare consumers. Therefore, any policy that helps lower costs should provide benefits for both patients as well as the healthcare industry overall. That’s why President Trump signed the initiative that required pharmaceutical companies to include drug prices in television advertisements.

“We are telling drug companies today: You’ve got to level with people [about] what your drugs cost,” Health and Human Services (HHS) Secretary Alex Azar (above) stated after Congress passed the President’s proposal, STATreported. “Put it in the TV ads. Patients have a right to know, and if you’re ashamed of your drug prices, change your drug prices. It’s that simple.” [Photo copyright: Washington Times.]

The controversial proposal, which would have applied to all prescription drugs that cost more than $35 for a one-month supply, was scheduled to go into effect over the summer until it was blocked by Federal Judge Amit Mehta of the US District Court for the District of Columbia.

Judge Mehta ruled that HHS does not have the regulatory power to force pharmaceutical companies to include the prices of prescription drugs in their TV ads and that the agency had violated laws passed by Congress.

“That policy very well could be an effective tool in halting the rising cost of prescription drugs. But no matter how vexing the problem of spiraling drug costs may be, HHS cannot do more than what Congress has authorized,” Mehta wrote in his decision, NPR reported.

Drug companies Amgen (NASDAQ:AMGN), Eli Lilly (NYSE:LLY) and Merck (NYSE:MRK) along with the Association of National Advertisers (ANA) filed lawsuits over the regulation stating it was a violation of their free speech rights. They won the reprieve on July 8, just one day before the regulation would have gone into effect.

Mehta stated in his opinion that the Social Security Act, which HHS used as its basis for the regulation, does not “empower HHS to issue a rule that compels drug manufacturers to disclose list prices,” Fierce Pharma reported.

In August, the Trump administration filed an appeal after the federal judge struck down the regulation. The exact basis for that appeal has not been disclosed. 

Drug Companies Decry New Law as Unconstitutional

Many drug makers are not happy with the rule. Drug industry trade group Pharmaceutical Research and Manufacturers of America (PhRMA) believes that mandating drug companies to disclose pricing in TV commercials is a violation of their First Amendment rights, STAT reported.

Nevertheless, PhRMA proposed that pharmaceutical companies provide a web link in their TV advertisements that directs consumers to pricing information online. And some companies also are experimenting with going a step further and voluntarily complying with the original regulation.

In a news release, PhRMA states, “To help patients make more informed healthcare decisions, [PhRMA] member companies today announced their commitment to providing more transparency about medicine costs. PhRMA member companies’ direct-to-consumer (DTC) television advertisements will soon direct patients to information about medicine costs, including the list price of the medicine, out-of-pocket costs, or other context about the potential cost of the medicine and available financial assistance. The biopharmaceutical industry will also launch a new platform that will provide patients, caregivers, and providers with cost and financial assistance information for brand-name medicines, as well as other patient support resources.”

However, Azar said that action is not in compliance with the rule. “They put $4 billion a year into television advertising because the television ad is where people are getting their information, and to point them to the internet would be the equivalent of saying that they should simply be putting their ads on the internet and not running them on TV,” he told the press, STAT reported.

Opponents of the rule noted that actual drug costs for consumers can vary widely depending on coverage and that patients might forgo their medications if they are concerned about the costs, reported Politico following passage of the measure in May.

Critics also claimed that that there were no enforcement mechanisms outlined for companies that did not comply with the ruling, and that it relied on the pharmaceutical industry to police itself. If a particular company failed to include the required information in its TV ads, competitors could file suit against it under the deceptive and unfair trade practice provisions of the Lanham Act, Politico noted.

Solutions to the public’s demand for price transparency in healthcare may be forthcoming. However, at press time, no further information concerning the status of this HHS regulation was available. Dark Daily will continue to monitor the situation and inform readers of any developments.

Meanwhile executives and pathologists at the nation’s clinical laboratories should continue to develop strategies to serve patients who want to know the prices of their medical laboratory tests before they arrive to have their specimens collected.

This summer, several pharma companies may have succeeded in getting a federal court to stop this particular rule to disclose prescription drug prices. But the trend toward price transparency has deep roots and will continue forward.

—JP Schlingman

Related Information:

Drug Makers Will Have to Include Prices in TV Ads as Soon as This Summer

Judge Blocks Trump Rule Requiring Pharma Companies to Disclose Drug Prices in TV Ads

Appeal Shows Trump’s HHS Isn’t Giving Up on Putting Drug Prices in TV Ads

Trump Finalizes Rule to Require Drug Prices in TV Ads

Johnson and Johnson Will List Drug Prices in TV Commercials

PhRMA Members Take New Approach to DTC Television Advertising

What You Need to Know about Putting Drug Prices in TV Ads

Why Putting List Prices in Drug Ads Matters

Proposed Federal Rules Let Patients Compare Healthcare Costs on Their Smartphones

Another push for price transparency steps up pressure on medical laboratories and anatomic pathology groups to develop compliance strategies

Clinical laboratories and anatomic pathology groups are under increasing pressure to develop strategies for making their test prices more accessible to patients. Those pressures are likely to grow due to newly proposed federal regulations that aim to allow patients to compare prices for healthcare services on their smartphones.

This new proposed rule comes less than a year after a rule involving hospital prices was implemented. As of January 1, 2019, the federal Centers for Medicare and Medicaid Services (CMS) required US hospitals to post their prices online. Dark Daily reported last year about the risks and opportunities posed by that move.

Now, new proposed rules published separately in March by CMS and also by the Office of the National Coordinator for Health Information Technology (ONC) focus on larger issues involving patient access to electronic health information (EHI). That includes empowering patients who want to compare healthcare costs, said Donald Rucker, MD, National Coordinator for Health Information Technology in a statement to the US Senate Committee on Health, Education, Labor and Pensions (HELP).

“In our current health system, there is an asymmetry of information for patients. They have few ways if any to anticipate or plan for costs, lower or compare costs, and, importantly, measure their quality of care or coverage relative to the price they pay. Transparency in the price and cost of healthcare could help address some of those concerns by empowering patients with information they need to make informed decisions,” said Donald Rucker, MD (above), National Coordinator for Health Information Technology (ONC), in remarks delivered to the US Senate. (Photo copyright: ONC.)

Giving Patients Access to Their Health Information

In May, officials with those agencies discussed the regulations in prepared remarks for a hearing of the HELP committee.

“A central purpose of the proposed [ONC] rule is to facilitate patient access to their EHI on their smartphone, growing a nascent patient- and provider-facing app economy,” he said, noting that this access is impeded by a lack of interoperability between health information systems, as well as restrictions on information exchange imposed by health IT developers.

The proposed rule will mandate use of common software standards so that app developers can access health information systems from different vendors. As a result, patients could choose their own apps to view their data regardless of which electronic health records (EHR) system their provider uses. The rule also includes provisions for dealing with so-called “information blocking” by vendors, Rucker noted.

If the proposed rule is implemented as currently written, there would be a need for clinical laboratories and pathology groups to ensure that their laboratory information systems (LIS) meet the specifications of the new rule. This may mean that, along with enabling two-way digital interfaces with physicians’ EHRs, labs also would need to be able to pass data to the apps and mobile devices used by patients that are covered by the proposed new rule.

“ONC’s proposed rule primarily focuses on clinical data,” he said. “However, advances in computer science and the maturity of data standards are accelerating the convergence of medical data with billing and price data. As such, the rule proposes to include such information as part of a patient’s EHI that should be available for access, exchange, and use.”

Enabling cost comparisons will allow patients to make more-informed decisions about their healthcare, Rucker added. But he acknowledged that implementing this vision won’t be easy.

“Unfortunately, the complex and decentralized nature of how payment information for healthcare services is currently created, structured, and stored presents many challenges to achieving price transparency,” he said. “This entire information chain is geared to retrospective payments rather than prices.”

Rucker told the HELP committee that the [ONC] will be seeking public input about how to capture price information and enable price transparency. Once the rule is finalized and published, providers will have two years to comply.

Medical Laboratories Need a Strategy for Providing Access to Patient Records

The proposed CMS rule imposes requirements on payers to provide electronic access to health claims and other information for their enrollees.

In her prepared remarks for the Senate HELP hearing, Kate Goodrich, MD, Director of the Center for Clinical Standards and Quality (CCSQ) and CMS Chief Medical Officer, said, “A core policy principle underlying our proposals is that every American should be able, without special effort or advanced technical skills, to see, obtain, and use all electronically available information that is relevant to their health, care, and choices—of plans, providers, and specific treatment options.”

That’s all well and good, however, as Fred Schulte, a senior correspondent for Kaiser Health News, wrote in his coverage of the two proposed rules, “Meeting these goals could prove to be a tall order.”

He continued, “For well over a decade, federal officials have struggled to set up a digital records network capable of widespread sharing of medical data and patient records.” Not to mention the billions of dollars already spent by the CMS and ONC incentivizing providers to implement truly interoperable health information exchange (HIE) systems nationwide.

Nevertheless, pressure for greater consumer data access and price transparency will likely continue to build across the healthcare industry, including on medical laboratories. Price transparency as a trend is making steady forward progress, despite resistance by hospitals, physicians, medical associations, and others.

All clinical laboratories should have a strategy to make lab test prices readily available to patients. It is something that will become common at some future point.

—Stephen Beale

Related Information:

Going Above and Beyond the CMS Hospital Price Transparency Rule

Proposed Rule by the Centers for Medicare and Medicaid Services on 03/04/2019

Proposed Rule by the Health and Human Services Department on 03/04/2019

Feds Want to Show Health Care Costs on Your Phone, But That Could Take Years

Latest Push by CMS for Increased Price Transparency Highlights Opportunities and Risks for Clinical Laboratories, Pathology Groups

Mount Sinai Health System Study Finds Use of AI-Enabled Monitoring System Improves Use of Blood During Childbirth

Study suggests AI-enabled technology can help clinical laboratories and hospital blood banks save thousands of dollars annually on expensive blood products

Artificial intelligence may prove to be a useful tool in helping hospitals better manage utilization of blood products. That’s one conclusion from a newly-published study done at New York’s Icahn School of Medicine at Mount Sinai. If so, this is a technology improvement that would be welcomed by blood bankers and clinical laboratory managers who must manage the cost and utilization of blood products.

There’s no way around it—blood is expensive. A typical 400- to 600-bed hospital likely budgets upwards of one million dollars annually just for blood products. Almost universally, in hospitals the medical laboratory manages the blood bank. This is where medical technologists trained in blood banking test patients and test blood to ensure whole blood units, or other blood products such as platelets, match and will not trigger a negative reaction when administered to the patient.

When left unmanaged, the cost and utilization of blood bank products can put the budgets of hospital medical laboratories in the red. Hospitals also invest a great deal of money training surgeons to accurately assess the procedure and order the correct amount of blood components prior to surgery.

Therefore, new artificial intelligence (AI) technology that helps pinpoint patients’ blood loss during childbirth will be of interest to blood bankers and hospital laboratory administrators.

Can AI Help Clinical Labs Improve Utilization of Blood Products in Hospitals?

Physicians at the Icahn School of Medicine at Mount Sinai recently investigated whether “Quantifying blood loss” would improve the use of blood during human childbirth. They published the results of their study in the International Journal of Obstetric Anesthesia.

Their research into 7,618 deliveries (vaginal and cesarean) involved “An observational study comparing blood loss, management, and outcomes between two historical cohorts (August 2016 to January 2017 and August 2017 to January 2018) at an academic tertiary care center. Patients in the intervention group (second period) had blood loss quantified compared with visual estimation for controls,” the research paper notes.

The researchers concluded that “Quantifying blood loss may result in increased vigilance for vaginal and cesarean delivery. We identified an association between quantifying blood loss and improved identification of postpartum hemorrhage, patient management steps, and cost savings.”

The researchers, according to a press release, employed the Triton AI-enabled platform from Gauss Surgical, a silicon valley-based health technology company, to “monitor blood loss in all deliveries (vaginal and cesarean, n=3807) at Mount Sinai Hospital from August 2017 through January 2018 to support the institution’s stage-based hemorrhage protocol.”

The researchers found that use of a monitoring system was associated with earlier postpartum hemorrhage intervention and annual cost savings of $172,614 in lab costs and $36,614 in blood bank costs.

Daniel Katz, MD (above), Director of Obstetric Anesthesia Research and Associate Professor Anesthesiology, Perioperative and Pain Medicine, at Mount Sinai Hospital in New York, said in the news release, “This study demonstrates that efficiently obtaining accurate, real-time blood loss information is critical to the successful implementation of a stage-based hemorrhage protocol.” Katz was the study’s lead author. (Photo copyright: Mount Sinai Hospital.)

Measuring Blood Loss: The Eye versus AI

Gauss has secured Food and Drug Administration (FDA) clearance for Triton and more than 50 US hospitals are using it. Triton provides, in real-time, images of blood-saturated surgical sponges and canisters and uses computer vision and machine learning to pinpoint blood loss, reported MD+DI.

Traditionally, physicians visually estimate blood loss during procedures. When they are off in their estimates of postpartum hemorrhage, harmful postpartum health complications and deaths can occur, the Mount Sinai researchers explained in their paper.

And although other vital signs—heart rate, rhythm, blood pressure, oxygen level, etc.— are monitored with equipment in the surgical suite, blood usage is not. 

“Blood loss in surgery has been an enigma for decades since the dawn of medicine,” Siddarth Satish, Founder and Chief Executive Officer of Gauss, told MD+DI. “We monitor many other vital signs in surgery, but ultimately there hasn’t been any direct indicator of a patient’s hemoglobin loss.”

Bleeding Better Recognized, Less Blood Transfusions

After the Mount Sinai researchers used the Triton system to monitor blood loss during 3,807 vaginal and cesarean deliveries from August 2017 to January 2018 at Mount Sinai Hospital, they compared their findings to 3,811 deliveries from August 2016 to January 2017, during which doctors relied solely on visual estimation of blood loss.

The study found the following, according to the news release:

  • Improved hemorrhage recognition in vaginal deliveries of 2.2% and cesarean sections of 12.6% compared to .5% and 6.4%, respectively;
  • Less blood transfusions needed (vaginal patients): 47% with Triton compared to 71%;
  • Reduced blood transfusion dose (cesarean section): 1.90 units with Triton compared to 2.52 units;
  • Cost savings: $209,228 a year (the total of aforementioned lab and blood bank costs).

“What we like about [Gauss] is that it somewhat embodies precision medicine in the sense that you’re using more precise tools of measurement in their first use case,” Garrett Vygantas, MD, MBA, Managing Director for OSF Ventures, the financing arm of OSF Healthcare, who also serves on Gauss Surgical’s board, told MD+DI.

Possible New Resource for Hospital Medical Laboratories

So, will AI quickly become an omnipresent overseer in surgical suites? Hardly. However, AI is in the early stages of finding places in healthcare where it can be useful.  “A lot of people are predicting that AI will play a huge role in healthcare … I think it’ll be ever-present. There will be a little bit of AI in everything you’re doing, but I think the actual practice of medicine in its truest form is going to carry forward,” Satish told Fierce Healthcare.

Hospital medical laboratories and blood blanks looking for new tools to manage blood use may want to look into AI-enabled systems like Triton. Saving money is not the only benefit. Less transfused blood is better for patient care as well. 

—Donna Marie Pocius

Related Information:

New Publication Concludes Gauss Surgical’s Triton System Associated with Earlier Postpartum Hemorrhage Intervention and Reduced Costs

The Association Between the Introduction of Quantitative Assessment of Postpartum Blood Loss and Institutional Changes in Clinical Practice: An Observational Study

Gauss Uses AI to Accurately Measure Blood Loss

Clinical Experience with the Implementation of Accurate Measurement of Blood Loss During Cesarean Delivery: Influences on Hemorrhage Recognition and Allogeneic Transfusion

Special Report: Gauss Surgical

Gauss Raises $20 Million in Series C from Northwell Health and Softbank Ventures Korea for AI-Enabled Platform for the Operating Room

Scientists in United Kingdom Manipulate DNA to Create a Synthetic Bacteria That Could Be Immune to Infections

Use of synthetic genetics to replicate an infectious disease agent is a scientific accomplishment that many microbiologists and clinical laboratory managers expected would happen

Microbiologists and infectious disease doctors are quite familiar with Escherichia coli (E. coli). The bacterium has caused much human sickness and even death around the globe, and its antibiotic resistant strains are becoming increasingly difficult to eradicate.

Now, scientists in England have created a synthetic “recoded” version of E. coli bacteria that is being used in a positive way—to fight disease. Their discovery is being heralded as an important breakthrough in the quest to custom-alter DNA to create synthetic forms of life that one day could be designed to fight specific infections, create new drugs, or produce tools to diagnose or treat disease.

Scientists worldwide working in the field of synthetic genomics are looking for ways to modify genomes in order to produce new weapons against infection and disease. This research could eventually produce methods for doctors—after diagnosing a patient’s specific strain of bacteria—to then use custom-altered DNA as an effective weapon against that patient’s specific bacterial infection.

This latest milestone is the result of a five-year quest by researchers at the Medical Research Council Laboratory of Molecular Biology (MRC-LMB) in Cambridge, England, to create a man-made version of the intestinal bacteria by redesigning its four-million-base-pair genetic code.

The MRC-LMB lab’s success marks the first time a living organism has been created with a compressed genetic code.

The researchers published their findings in the journal Nature.

Synthetic Genomics and Clinical Laboratories

Benjamin A. Blount, PhD, a postdoctoral research associate at Imperial College London, and Tom Ellis, PhD, Professor in Synthetic Genome Engineering at Imperial College London, praised the MRC-LMB team’s accomplishment in a subsequent Nature article.

“This is a landmark in the emerging field of synthetic genomics and finally applies the technology to the laboratory’s workhorse bacterium,” they wrote. “Synthetic genomics offers a new way of life, while at the same time moving synthetic biology towards a future in which genomes can be written to design.”

All known forms of life on Earth contain 64 codons—a specific sequence of three consecutive nucleotides that corresponds with a specific amino acid or stop signal during protein synthesis. Jason Chin, PhD, Program Lead at MRC-LMB, said biologists long have questioned why there are 20 amino acids encoded by 64 codons.

“Is there any function to having more than one codon to encode each amino acid?” Chin asked during an interview with the Cambridge Independent. “What would happen if you made an organism that used a reduced set of codons?”

The MRC-LMB research team took an important step toward answering that question. Their synthetic E. coli strain, dubbed Syn61, was recoded through “genome-wide substitution of target codons by defined synonyms.” To do so, researchers mastered a new piece-by-piece technique that enabled them to recode 18,214 codons to create an organism with a 61-codon genome that functions without a previously essential transfer RNA.

“Our synthetic genome implements a defined recoding and refactoring scheme–with simple corrections at just seven positions–to replace every known occurrence of two sense codons and a stop codon in the genome,” lead author Julius Fredens, PhD, a post-doctoral research associate at MRC, and colleagues, wrote in their paper.

Science Alert reports that the laboratory-created version of E. coli (above) “isn’t quite a dead ringer for its ancestor. The cells are a touch longer, and they reproduce 1.6 times slower. But the edited E. coli seems healthy and produces the same range and quantity of proteins as the non-edited versions.” (Photo copyright: Jason Chin/STAT.)

Joshua Atkinson, PhD, a postdoctoral research associate at Rice University in Houston, labeled the breakthrough a “tour de force” in the field of synthetic genomics. “This achievement sets a new world record in synthetic genomics by yielding a genome that is four times larger than the pioneering synthesis of the one-million-base-pair Mycoplasma mycoides genome,” he stated in Synthetic Biology.

“Synthetic genomics is enabling the simplification of recoded organisms; the previous study minimized the total number of genes and this new study simplified the way those genes are encoded.”

Manmade Bacteria That are Immune to Infections

Researchers from the J. Craig Venter Institute in Rockville, Maryland, created the first synthetic genome in 2010. According to an article in Nature, the Venter Institute successfully synthesized the Mycoplasma mycoides genome and used it “reboot” a cell from a different species of bacterium.

The MRC-LMB team’s success may prove more significant.

“This new synthetic E. coli should not be able to decode DNA from any other organism and therefore it should not be possible to infect it with a virus,” the MRC-LMB stated in a news release heralding the lab’s breakthrough. “With E. coli already being an important workhorse of biotechnology and biological research, this study is the first time any commonly used model organism has had its genome designed and fully synthesized and this synthetic version could become an important resource for future development of new types of molecules.”

Because the MRC-LMB team was able to remove transfer RNA and release factors that decode three codons from the E. coli bacteria, their achievement may be the springboard to designing manmade bacteria that are immune to infections or could be turned into new drugs.

“This may enable these codons to be cleanly reassigned and facilitate the incorporation of multiple non-canonical amino acids. This greatly expands the scope of using non-canonical amino acids as unique tools for biological research,” the MRC-LMB news release added.

Though synthetic genomics impact on clinical laboratory diagnostics is yet to be known, medical laboratory leaders should be mindful of the potential for rapid innovation in this field as proof-of-concept laboratory innovations are translated into real-world applications.

—Andrea Downing Peck

Related Information:

Scientists Redesigned an Entire Genome to Create the Most Synthetic Life Form Yet

World’s First Synthetic Organism with Fully Recoded DNA Is Created at MRC LMB in Cambridge

Creating an Entire Bacterial Genome with a Compressed Genetic Code

Total Synthesis of Escherichia Coli with a Recoded Genome

Construction of an Escherichia Coli Genome with Fewer Codons Sets Records

Life Simplified: Recompiling a Bacterial Genome for Synonymous Codon Compression

Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome

Cambridge University Researchers Recode E. Coli DNA to Create Living, Reproducing Bacteria with Entirely Synthetic DNA

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